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As Arrhidaeus grew older it became apparent that he had mild learning difficulties.
Plutarch was of the view that he became disabled by means of an attempt on his life by Philip II's wife, Queen Olympias, who wanted to eliminate a possible rival to her son, Alexander, through the employment of pharmaka (drugs/spells); however, most modern authorities doubt the truth of this claim., both to protect his life and to prevent his use as a pawn in any prospective challenge for the throne.
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An opportunity presented itself in 317 BC when Cassander expelled Polyperchon from Macedonia.
Arrhidaeus' whereabouts during the reign of his brother Alexander are unclear from the extant sources; what is certain is that no civil or military command was given to him in those thirteen years (336–323 BC).
He was in Babylon at the time of Alexander's death on 10 June 323 BC. Arrhidaeus was the most obvious candidate, but he was mentally unfit to rule.
Eurydice immediately allied herself with Cassander and persuaded her husband to nominate him as the new regent.
Cassander reciprocated by leaving her in full control of the country when he left to campaign in Greece.