On the other side of the river there lay a large and fertile province called Quiqualtanqui, the cacique of which was a haughty warlike youth, who believed that although the Spaniards were now building vessels to convey them out of the country, they might yet return in greater numbers to enslave the natives. For this reason he determined to destroy them, and assembled forces from all parts of the country, both those of his, own tribe and from all the tribes around. Having concluded an extensive confederacy and begun his preparations for war, he sent a friendly message to Alvarado to lull him into security, advising all his confederates to do the same. The general gave them all favourable answers, yet kept himself carefully on his guard. Quiqualtanqui invited Anilco to join in the confederacy, instead of which he gave notice of it to the Spaniards. It was not known how Guachacoya stood affected on this occasion, but he was suspected of having hostile intentions, as he made no communication of the conspiracy. The confederates continued to send frequent messages and presents to the Spaniards to discover what they were doing; and though repeatedly warned not to come to their quarters under night they took no notice of it. One night that Gonzalo Silvestre happened to stand centinel in the second watch, the moon shining very bright, he observed two armed Indians in their plumes of feathers, passing over the ditch on a tree that lay across instead of a bridge. These men came to a postern which they entered without asking leave, on which Silvestre gave one of them a cut on the forehead, on which he immediately fled. The other Indian, without waiting for his wounded companion, got into the canoe on the river and gave the alarm to his party. The wounded man, missing the tree across the ditch, swam over and cried out for assistance when he came to the river, on which some of his friends came and carried him off. At sunrise, Quiqualtanqui sent four messengers demanding that Alvarado should punish the centinel for having been guilty of a breach of the peace, more especially, as the wounded man was a chief. Four other messengers arrived at mid-day on a similar errand, saying that the wounded chief was at the point of death; and four more came in the afternoon affirming that he was dead, and insisted that the centinel should be publicly punished, since the action he had committed was an affront to all the Indians of the confederacy. Alvarado boldly answered, that they had been previously and repeatedly warned never to come to the Spanish quarters under night, being always welcome and honourably treated through the day. He added that though sincerely sorry for what had happened, he could not possibly punish the centinel who had only done his duty according to military discipline, neither would his soldiers allow of any such thing being done. The confederates thought fit to connive at this transaction, satisfied that Alvarado was a man of invincible courage and wise conduct; yet resolved upon executing their design against the Spaniards as soon as possible.

Being eager to get away from the country, the Spaniards laboured indefatigably in fitting out the vessels, even the best gentlemen among them using the utmost diligence; while those who were not handy in the several occupations about the brigantines employed themselves in hunting and fishing to procure provisions for the rest. Among other fish taken on the present occasion, one was taken by means of a hook of such enormous dimensions, that the head alone weighed forty pounds. The confederate Indians under Quiqualtanqui continued their warlike preparations, being much encouraged by knowing that Ferdinand de Soto was dead, that the number of the Spaniards was very much diminished, and that very few horses were left. So confident were they of success, that two of their spies desired some of the Indian women who served the Spaniards to be patient, for they would soon be freed from their bondage to these vagabond robbers, as they were all to be slain. But the women disclosed this to their masters. When the night happened to be very still, the noise of many people could be heard from the opposite side of the river; and the Spaniards could distinctly see numerous fires at regular distances, as of the quarters of a large army. But it pleased God to confound the evil designs of these Indians, by an inundation of the river, which began on the 10th of March 1543, and increased with prodigious rapidity, so that on the 18th which was Palm Sunday, when the Spaniards were in procession, for they observed all the religious solemnities, the water broke in at the gates of the town, and there was no going along the streets for long after but in canoes. This inundation was forty days of rising to its greatest height, which was on the 20th of April, at which time it extended above twenty leagues on each side of the river, so that nothing could be seen in all the country around but the tops of the trees, and the people had to go every where in canoes.

During the time of this terrible inundation, Alvarado sent twenty Spaniards to Anilco to request a supply of rosin, blankets, and cordage for completing the equipment of the vessels, and these men were sent in four canoes lashed two and two together, to prevent them from being overset by the trees which were under water. On coming to the town of Anilco, they found it destroyed, though twenty leagues from the Spanish quarters, and the inundation had extended five leagues farther. Gonzado Silvestre who commanded these Spaniards was greatly in favour of the cacique Anilco, because he had restored to him a youth who had accompanied the Spaniards on their march to the westwards, who perfectly understood the Spanish language, and was so much attached to the Spaniards as to be very averse from returning to his father. On this occasion Anilco supplied Silvestre with every thing of which he was in want.

It pleased God that the water began to subside towards the latter end of April; yet so slowly that on the 10th of May there was no going about the streets of the town on account of the deep mire with which they were filled. This was the more distressing to the Spaniards as they were barefooted, all their shoes having been burnt at Mavila, and the shoes they had since been able to make, being of untanned leather, were like so much tripe as soon as wet. At the latter end of May, the great river returned to its usual channel, and the confederated Indians again drew their forces together to execute their original design against the Spaniards, of which they received intelligence from Anilco; who likewise informed Alvarado of the signals which had been concerted by the confederates for the better prosecution of their enterprise, and even offered to assist the Spaniards with 8000 well armed warriors, and that if they chose to retire into his country the confederates would not dare to attack them. Alvarado returned thanks for these friendly offers, but declined accepting them; because as he intended to go down the river and to quit the country, he did not deem it proper either to take refuge in the territory of Anilco or to accept the assistance of his warriors, as either of those might draw upon him the confederated hostility of his neighbours: But he promised, if it should please God ever to put it in his power, Anilco should not have cause to repent the service he had been of to the king of Spain, or the kindness he had shewn to the Spaniards. In conclusion, he recommended to Anilco to discontinue any farther intercourse with him, lest he might give umbrage to the confederated caciques. Many of the Spaniards were so puffed up by the friendly offers of Anilco, that they endeavoured to persuade Alvarado to accept the proferred aid, and prosecute an offensive war, thinking it easy to subdue these people. But Alvarado was quite sensible of his present weakness, and determined to leave the country as soon as possible; besides which he did not deem it prudent to confide too much on the fidelity of Anilco.