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Arguably, Macbeth's fatal flaw is his ambition, which, it is suggested in Act I scene 3, has already caused him to think about murdering Duncan and seizing the crown. This is something that makes him easy prey for the witches and their manipulation and prophecies. What makes Macbeth's downfall even more tragic, however, is the way that he recognises that ambition is his own tragic flaw, but then leaves himself open to the manipulation of another character--this time his own wife. Note what he says in his soliloquy in Act I scene 7:
I have no spur
To prick the sides of my intent, but only
Vaulting ambition, which o'erleaps itself
And falls on th'other--
The image is of somebody who tries to mount a horse so enthusiastically, that they end of missing the horse completely and landing on the floor on the other side. So too, Macbeth sees the danger of himself trying to achieve more than he can reasonably gain through his ambition, and hurting himself in the process. The irony is of course that Macbeth is correct: he ends up losing far more than he ever had. However, it is his ambition to not only be King of Scotland, but then also to ensure that he does not lose that title for his descendants, that drives him to his various excesses.
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