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Cassander's refusal to accept his father's decision sparked the Second War of the Diadochi, in which Eurydice saw once again a chance to free Philip from the control of the regent.

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.

After Alexander's death in Babylon in 323 BC, the Macedonian army in Asia proclaimed Arrhidaeus as king; however, he served merely as a figurehead and as the pawn of a series of powerful generals.

Even though Arrhidaeus and Alexander were about the same age, Arrhidaeus appears never to have been a danger as an alternative choice for Alexander's succession to Philip II; nevertheless, when the Persian satrap of Caria, Pixodarus, proposed his daughter in marriage to Philip, the king declined, offering his son Arrhidaeus as husband instead, and Alexander thought it prudent to block the dynastic union (which might have produced a possible future heir to Philip's domain before Alexander himself did), resulting in considerable irritation on the part of his father (337 BC).

The reaction among the troops generated by this murder was such that the regent had to give up his opposition to the proposed match and accept the marriage. Eurydice moved deftly enough to achieve the removal of the first two designated regents, Peithon and Arrhidaeus (a namesake of her husband), but was powerless to block the aspirations of Antipater, whose position proved too powerful, and the latter was made the new regent; Philip Arrhidaeus and Eurydice were forced to follow Antipater back to Macedonia.

From that moment on, Philip Arrhidaeus was to be under the sway of his bride, a proud and determined woman bent on substantiating her husband's power. The regent died of natural causes the following year, nominating as his successor not his son Cassander, but his friend and lieutenant, Polyperchon.

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