The question of why Alexander the Great died at 32 has generated serious historical and medical debate since antiquity. Ancient sources offered several explanations: heavy drinking, poison, illness following a river journey in Babylonia. Modern medical historians have proposed typhoid fever, West Nile virus, alcohol-related pancreatitis, and even autoimmune disease.

A 2019 paper proposed a particularly striking hypothesis: Alexander may have suffered from Guillain-Barré syndrome, a neurological condition that can cause ascending paralysis while leaving the patient alert and aware. This would explain the ancient reports that his body showed no signs of decomposition for six days after death — he may not have been dead. The ancient sources describe symptoms consistent with ascending paralysis: weakness in the limbs, difficulty speaking.

The poison hypothesis has never disappeared. Alexander's death occurred at a convenient moment for several people: Antipater, his regent in Macedonia; the Macedonian officers who opposed his policy of integrating Persian nobles; even Aristotle has been named, though the evidence is thin. Forensic analysis of ancient wine residue from Macedonian contexts suggests that veratrum album (white hellebore) was known and potentially used as poison.

What is certain is that Alexander's death immediately triggered the catastrophic wars of the successors that dismembered his empire. The problem of succession — he left no adult heir and had not clearly designated a successor — made his death politically explosive regardless of its cause.