A more serious war was impending in Asia - a war which appeared of a very hazardous character on account not so much of the enemy as of the great distance and the insecurity of the communications with home, while yet, owing to the short-sighted obstinacy of Antiochus, the struggle could not well be terminated otherwise than by an attack on the enemy in his own country. The first object was to secure the sea. The Roman fleet, which during the campaign in Greece was charged with the task of interrupting the communication between Greece and Asia Minor, and which had been successful about the time of the battle at Thermopylae in seizing a strong Asiatic transport fleet near Andros, was thenceforth employed in making preparations for the crossing of the Romans to Asia next year and first of all in driving the enemy's fleet out of the Aegean Sea. It lay in the harbour of Cyssus on the southern shore of the tongue of land that projects from Ionia towards Chios; thither in search of it the Roman fleet proceeded, consisting of 75 Roman, 24 Pergamene, and 6 Carthaginian, decked vessels under the command of Gaius Livius. The Syrian admiral, Polyxenidas, a Rhodian emigrant, had only 70 decked vessels to oppose to it; but, as the Roman fleet still expected the ships of Rhodes, and as Polyxenidas relied on the superior seaworthiness of his vessels, those of Tyre and Sidon in particular, he immediately accepted battle. At the outset the Asiatics succeeded in sinking one of the Carthaginian vessels; but, when they came to grapple, Roman valour prevailed, and it was owing solely to the swiftness of their rowing and sailing that the enemy lost no more than 23 ships. During the pursuit the Roman fleet was joined by 25 ships from Rhodes, and the superiority of the Romans in those waters was now doubly assured. The enemy's fleet thenceforth kept the shelter of the harbour of Ephesus, and, as it could not be induced to risk a second battle, the fleet of the Romans and allies broke up for the winter; the Roman ships of war proceeded to the harbour of Cane in the neighbourhood of Pergamus. Both parties were busy during the winter in preparing for the next campaign. The Romans sought to gain over the Greeks of Asia Minor; Smyrna, which had perseveringly resisted all the attempts of the king to get possession of the city, received the Romans with open arms, and the Roman party gained the ascendency in Samos, Chios, Erythrae, Clazomenae, Phocaea, Cyme, and elsewhere. Antiochus was resolved, if possible, to prevent the Romans from crossing to Asia, and with that view he made zealous naval preparations - employing Polyxenidas to fit out and augment the fleet stationed at Ephesus, and Hannibal to equip a new fleet in Lycia, Syria, and Phoenicia; while he further collected in Asia Minor a powerful land army from all regions of his extensive empire. Early next year (564) the Roman fleet resumed its operations. Gaius Livius left the Rhodian fleet - which had appeared in good time this year, numbering 36 sail - to observe that of the enemy in the offing of Ephesus, and went with the greater portion of the Roman and Pergamene vessels to the Hellespont in accordance with his instructions, to pave the way for the passage of the land army by the capture of the fortresses there. Sestus was already occupied and Abydus reduced to extremities, when the news of the defeat of the Rhodian fleet recalled him. The Rhodian admiral Pausistratus, lulled into security by the representations of his countryman that he wished to desert from Antiochus, had allowed himself to be surprised in the harbour of Samos; he himself fell, and all his vessels were destroyed except five Rhodian and two Coan ships; Samos, Phocaea, and Cyme on hearing the news went over to Seleucus, who held the chief command by land in those provinces for his father.

But when the Roman fleet arrived partly from Cane, partly from the Hellespont, and was after some time joined by twenty new ships of the Rhodians at Samos, Polyxenidas was once more compelled to shut himself up in the harbour of Ephesus. As he declined the offered naval battle, and as, owing to the small numbers of the Roman force, an attack by land was not to be thought of, nothing remained for the Roman fleet but to take up its position in like manner at Samos. A division meanwhile proceeded to Patara on the Lycian coast, partly to relieve the Rhodians from the very troublesome attacks that were directed against them from that quarter, partly and chiefly to prevent the hostile fleet, which Hannibal was expected to bring up, from entering the Aegean Sea. When the squadron sent against Patara achieved nothing, the new admiral Lucius Aemilius Regillus, who had arrived with 20 war-vessels from Rome and had relieved Gaius Livius at Samos, was so indignant that he proceeded thither with the whole fleet; his officers with difficulty succeeded, while they were on their voyage, in making him understand that the primary object was not the conquest of Patara but the command of the Aegean Sea, and in inducing him to return to Samos. On the mainland of Asia Minor Seleucus had in the meanwhile begun the siege of Pergamus, while Antiochus with his chief army ravaged the Pergamene territory and the possessions of the Mytilenaeans on the mainland; they hoped to crush the hated Attalids, before Roman aid appeared. The Roman fleet went to Elaea and the port of Adramytium to help their ally; but, as the admiral wanted troops, he accomplished nothing. Pergamus seemed lost; but the laxity and negligence with which the siege was conducted allowed Eumenes to throw into the city Achaean auxiliaries under Diophanes, whose bold and successful sallies compelled the Gallic mercenaries, whom Antiochus had entrusted with the siege, to raise it. In the southern waters too the projects of Antiochus were frustrated. The fleet equipped and led by Hannibal, after having been long detained by the constant westerly winds, attempted at length to reach the Aegean; but at the mouth of the Eurymedon, off Aspendus in Pamphylia, it encountered a Rhodian squadron under Eudamus; and in the battle, which ensued between the two fleets, the excellence of the Rhodian ships and naval officers carried the victory over Hannibal's tactics and his numerical superiority. It was the first naval battle, and the last battle against Rome, fought by the great Carthaginian. The victorious Rhodian fleet then took its station at Patara, and there prevented the intended junction of the two Asiatic fleets. In the Aegean Sea the Romano-Rhodian fleet at Samos, after being weakened by detaching the Pergamene ships to the Hellespont to support the land army which had arrived there, was in its turn attacked by that of Polyxenidas, who now numbered nine sail more than his opponents. On December 23 of the uncorrected calendar, according to the corrected calendar about the end of August, in 564, a battle took place at the promontory of Myonnesus between Teos and Colophon; the Romans broke through the line of the enemy, and totally surrounded the left wing, so that they took or sank 42 ships. An inscription in Saturnian verse over the temple of the Lares Permarini, which was built in the Campus Martius in memory of this victory, for many centuries thereafter proclaimed to the Romans how the fleet of the Asiatics had been defeated before the eyes of king Antiochus and of all his land army, and how the Romans thus "settled the mighty strife and subdued the kings". Thenceforth the enemy's ships no longer ventured to show themselves on the open sea, and made no further attempt to obstruct the crossing of the Roman land army.