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Southern Italy

Totila marched south, where Roman garrisons were few and weak, bypassing Rome. The provinces of southern Italy were forced to recognise his authority. This campaign was one of rapid movement to take control of the countryside, leaving the Byzantines in control of isolated strongholds, mostly on the coast, which could be reduced later. When a fortified location fell, its walls were usually razed so that it would no longer be of any military value. Totila followed a policy of treating his captives well, enticing opponents to surrender rather than resist to the end. He also tried to win over the Italian population, exemplified by Totila's behaviour during the Siege of Naples, where he allowed the city to surrender on terms in 543 and displayed, in the words of J. B. Bury, "considerable humanity" in his treatment of the defenders. He nursed the famished citizens back to strength after allowing the Byzantine garrison safe departure. Having captured Naples, Totila attempted to broker a peace with Justinian. When this was refused he had copies of his appeal posted throughout Rome; despite the disfavour in which the Byzantines were held, there was no uprising in Totila's favour, which disgusted him. He marched north and besieged the city.

Taking advantage of a five-year truce in the East, Belisarius was sent back to Italy with 200 ships in 544. He successfully reoccupied much of southern Italy, but, according to Procopius, he was starved of supplies and reinforcements by a jealous Justinian and so felt unable to march to Rome's relief. Procopius describes famine during the siege, in which the ordinary Romans, who were not rich enough to buy grain from the military, were reduced to eating bran, nettles, dogs, mice and finally "each other's dung". Pope Vigilius, who had fled to the safety of Syracuse, sent a flotilla of grain ships, but Totila's navy intercepted them near the mouth of the Tiber and captured them. A desperate attempt by Belisarius to relieve Rome came close to success but ultimately failed. According to Procopius, the plan involved sailing a force up the river Tiber, destroying the temporary bridge and watchtowers constructed by Totila's forces by dropping a boat filled with flammable materials onto a watchtower from a makeshift tower built on top of two fastened skiffs, which succeeded. Afterwards, his subordinate Isaakes, ordered to remain in the city of Portus, heard of his early successes and took a cavalry force to attack the Gothic stockade, eager to share the glory. This resulted in his capture and, once the news of this reached Belisarius, he interpreted the news as Portus had been captured by the Goths, meaning he had lost the only allied settlement close by, and that his wife, present in the city, was now a hostage of the Goths. Said to have been struck with a bout of aphasia, he called for a retreat to immediately retake Portus, only to discover that it remained under Roman control. After more than a year Totila finally entered Rome on 17 December 546, when his men scaled the walls at night and opened the Porta Asinaria. Procopius states that Totila was aided by some Isaurian troops from the imperial garrison who had arranged a secret pact with the Goths. Rome was plundered and Totila, who had expressed an intention to completely level the city, satisfied himself with tearing down about one third of the walls. He then left in pursuit of the Byzantine forces in Apulia.

On Belisarius' absence during the reoccupation of Rome by the Goths, there are two opposing accounts: Procopius states that, upon discovering his mistake regarding Portus, he was overcome with a bout of depression and severe sickness which nearly resulted in his death. Jordanes, on the other hand, claims that he was recalled to Rome due to the death of the empress Theodora, and cites his absence as having emboldened Totila to recapture the city. Belisarius successfully reoccupied Rome four months later in the spring of 547 and hastily rebuilt the demolished sections of wall by piling up the loose stones "one on top of the other, regardless of order". Totila returned, but was unable to overcome the defenders. Belisarius did not follow up his advantage. Several cities, including Perugia, were taken by the Goths, while Belisarius remained inactive and was then recalled from Italy.

In 549, Totila advanced again against Rome. He attempted to storm the improvised walls and overpower the small garrison of 3,000 men, but was beaten back. He then prepared to blockade the city and starve out the defenders, although the Byzantine commander Diogenes had previously prepared large food stores and had sown wheat fields within the city walls. However, Totila was able to suborn part of the garrison, who opened the Porta Ostiensis gate for him. Totila's men swept through the city, killing all but the women, who were spared on the orders of Totila, and looting what riches remained. Expecting the nobles and the remainder of the garrison to flee as soon as the walls were taken, Totila set traps along the roads to neighboring towns that were not yet under his control and many were killed while fleeing Rome.