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After his first murder, Macbeth is wracked with guilt and remorse. He claims he will be unable to sleep ("Macbeth wil sleep no more" and "Macbeth hath murdered sleep"). The motif of the inability to sleep plays out throughout the remainder of the scene (II,2) after the killing of Duncan. In addition to being sure he will never sleep, Macbeth also believes he will never be cleansed of guilt--he claims that all the water in the ocean could not cleanse his hands of the blood. This is, of course, hyperbole (exaggeration), but the act of washing represents cleansing of sin and guilt; Macbeth believes his guilt cannot be purged. He says he would take back the murder if he could.
However, as Macbeth kills more (next the guards--who are covered with blood in the attempt to cast suspicion on them), he feels less and less guilty. If anything, the psychological effect of the successive killings is to make him want to kill even more. He even says at one point, "We are but young in deed" (that is, "we haven't even begun to do all the killing we will"). When he is unable to kill Macduff because Macduff has gone to England, he has Macduff's wife, her children, and the whole household killed. He becomes inured to killing and more monstrous. There is a glimpse of regret in Act V, after Macbeth learns of the death of his wife. He says "My way of life has fall'n into the sear" (he is getting older) but that he will not have the honor, respect, and love that should come to one in later life. But these words of regret are momentary, and Macbeth fights to the death until he succumbs to Macduff.
When he is unable to kill Fleance (after killing his friend Banquo), Macbeth revisits the witches to gather more confidence. But when they give him a prophecy he doesn't like (that the heirs of Banquo, not Macbeth, will reign in the future), he tries to thwart that prophecy while allowing the witches' prophetic riddles to make him overconfident. In several places throughout the play, Macbeth even prays to the dark spirits to give him the strength to be murderous and evil.
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