Macedonians and local residents wept at the news of the death, while Achaemenid subjects shaved their heads. The mother of Darius III, Sisygambis, having learned of Alexander's death, refused sustenance and died a few days later. Historians vary in their assessments of primary sources about Alexander's death, which results in different views.
In February 323 BC, Alexander ordered his armies to prepare for the march to Babylon. According to Arrian, after crossing the Tigris Alexander was met by Chaldeans, who advised him not to enter the city because their deity Bel had warned them that to do so at that time would be fatal for Alexander. The Chaldeans also warned Alexander against marching westwards as he would then look to the setting sun, a symbol of decline. It was suggested that he entered Babylon via the Royal Gate, in the western wall, where he would face to the east. Alexander followed this advice, but the route turned to be unfavorable because of swampy terrain. According to Jona Lendering, "it seems that in May 323" the Babylonian astrologers tried to avert the misfortune by substituting Alexander with an ordinary person on the Babylonian throne, who would take the brunt of the omen. The Greeks, however, did not understand that ritual.
Calanus was likely to be a Hindu Naga sadhu, whom Greeks called gymnosophists. He had accompanied the Greek army back from Punjab, upon request by Alexander. He was seventy-three years of age at that time. However, when Persian weather and travel fatigue weakened him, he informed Alexander that he would rather die than live disabled. He decided to take away his life by self-immolation. Although Alexander tried to desist him from doing so but upon the insistence of Calanus, Alexander relented and the job of building a pyre was entrusted to Ptolemy. The place where this incident took place was Susa in the year 323 B.C. Calanus is mentioned also by Alexander's admiral, Nearchus and Chares of Mytilene. He did not flinch as he burnt to the astonishment of those who watched. Before immolating himself alive on the pyre, his last words to Alexander were "We shall meet in Babylon". Thus he is said to have prophesied the death of Alexander in Babylon. At the time of the death of Calanus, Alexander, however, did not have any plan to go to Babylon. No one understood the meaning of his words "We shall meet in Babylon". It was only after Alexander fell sick and died in Babylon, that the Greeks came to realize what Calanus intended to convey.
Proposed causes of Alexander's death included alcoholic liver disease, fever, and strychnine poisoning, but little data support those versions. According to the University of Maryland School of Medicine report of 1998, Alexander probably died of typhoid fever (which, along with malaria, was common in ancient Babylon). In the week before Alexander's death, historical accounts mention chills, sweats, exhaustion and high fever, typical symptoms of infectious diseases, including typhoid fever. According to David W. Oldach from the University of Maryland Medical Center, Alexander also had "severe abdominal pain, causing him to cry out in agony". The associated account, however, comes from the unreliable Alexander romance. According to Andrew N. Williams and Robert Arnott, in Alexander the Great's last days he became mute. He became mute because of a previous injury to his neck from the Siege of Cyropolis.
Other popular theories hold that Alexander either died of malaria or was poisoned. Other retrodiagnoses include noninfectious diseases as well. According to author Andrew Chugg, there is evidence Alexander died of malaria, having contracted it two weeks before his death while sailing in the marshes to inspect flood defences. Chugg based his argument on Ephemerides by otherwise unknown Diodotus of Erythrae, although the authenticity of this source has been questioned. It was also noted that the absence of the signature fever curve of Plasmodium falciparum (the expected parasite, given Alexander's travel history) diminishes the possibility of malaria. The malaria version was nonetheless supported by Paul Cartledge.