After hearing the prophecy of the three witches, Macbeth contemplates in his "vaulting ambition" the murder of Duncan. Lady Macbeth has planned to commit this act, but because Duncan resembles her father, she delegates Macbeth for the commitment of the heinous deed. With certain misgivings because Duncan has always been virtuous and he owes him loyalty, Macbeth, nevertheless responds to the ringing of the bell and slays the king. Upon his return, Macbeth tells his wife that the guards cried out "Murder" and later "God bless us!" to which he could not respond "Amen." Further, he tells her that he heard someone call out, "Macbeth shall sleep no more." But Lady Macbeth suggests that her husband forget such things and get some water to wash away "this filthy witness" (2.2.60) of the blood from his hands. She tells him he weakens his noble strength by thinking of such things, and scolds Macbeth for bringing the daggers with him, telling him to return them. But, Macbeth is too disturbed to return; so, Lady Macbeth takes the daggers, smearing blood upon the faces of the guards.

After his wife leaves, Macbeth hears knocking:

Whence is that knocking?
How is't with me, when every noise appals me?
What hands are here? Ha, they pluck out mine eyes!(75)
Will all great Neptune's ocean wash this blood
Clean from my hand? No, this my hand will rather
The multitudinous seas incarnadine,
Making the green one red. (2.2.73-79)

Here Macbeth becomes nervous and wonders why every little noice makes him jump. Looking down at his hands, Macbeth says that they pluck out his eyes. This may be an allusion to Oedipus Rex, who in his guilt and shame blinded himself. For, Macbeth feels such tremendous guilt that he says that Neptune's great ocean cannot wash the blood/guilt from his hands. He has so much guilt—blood—on his hands that he would turn the sea red.