The frescoes of the Egyptian story of Isis, Osiris and the bull Apis that were painted by Pinturicchio and workshop on ceilings in the Vatican Palace in 1493 have attracted attention, particularly since the rooms were restored in the late 1890s. That they were commissioned for Rodrigo Borgia (1431-1503) for a room, the Sala dei Santi, in his private suite, the Appartamento Borgia, shortly after he became Pope Alexander VI in August 1492, has added to speculation as to how they should be interpreted. It has been widely held that they were inspired by Annius of Viterbo (1424-1502), a Dominican monk and fraudster, because a few years later he included a similar story in a genealogy of Pope Alexander VI. Leading interpretations have assumed Annius' involvement and have suggested that the story was chosen for these frescoes because the Borgia emblem incorporated a bull, or to reflect the Ottoman threat to the Church. This thesis demonstrates that Annius could not have inspired these frescoes and thus challenges previous interpretations. By considering who else might have inspired this theme it proposes an alternative interpretation. The Venetian humanist Ermolao Barbaro (1454-1493) was well positioned to have been involved. In May 1490 he had visited Marsilio Ficino (1433-1499) who had recently been translating the Neoplatonist Plotinus' works relating to daímones, intermediaries between man and the gods. Plutarch's account of the Isis and Osiris myth, knowledge of which would have been necessary to have specified the detail of the frescoes, casts Isis and Osiris as daímones. It is proposed that these frescoes depict an allegory of intermediation with the gods as part of a theurgical programme of syncretising Christianity with ancient religions, and that the central figure in the largest wall fresco in the room is a portrayal of Plotinus.