On the night of Duncan's murder, Macbeth exits the king's chamber with bloody hands, seemingly even more anxious over the deed than he was before he committed it. Macbeth experiences auditory hallucinations and struggles to compose himself. In his daze, he has forgotten to plant the bloody daggers he used on Duncan on the sleeping guards, whom the Macbeths intend to frame for the king's murder. Frustrated, Lady Macbeth criticizes Macbeth's panic and proceeds to place the bloody daggers by the guards herself, smearing the blood on their bodies to make it seem like they attacked the king.

Once Lady Macbeth exits Duncan's chamber, Macbeth laments over the blood on his hands, and Lady Macbeth criticizes him for being so weak, remarking that her hands are (metaphorically) just as bloody as his ("My hands are of your color, but I shame / To wear a heart so white"). Blood is a major motif in the play, and the blood on Macbeth's hands is not only evidence of his violent crime, but a symbolic representation of the stain such a crime leaves on the soul. Having been instrumental in urging Macbeth to kill the king, Lady Macbeth's hands, too, are bloody. Unlike her husband, however, she feels no remorse or regret over her actions.

As the play progresses, Lady Macbeth seems to experience delayed guilt for their crime. She gradually begins to lose her mind and is tortured by hallucinations (much like her husband was in the moments before and after Duncan's murder). In the grip of madness, Lady Macbeth begins to sleepwalk and wrings her hands, as if trying to wash them. As Lady Macbeth rubs her hands, she famously says, "Out, damned spot! Out, I say!" No matter how she tries, she cannot cleanse the blood from her hands, symbolizing her inability to rid herself of the guilt that torments her.

Lady Macbeth's hallucinations echo Macbeth's earlier remark: "Will all great Neptune’s ocean wash this blood / Clean from my hand?" While Macbeth seemingly loses his conscience entirely after Duncan's death, Lady Macbeth appears to develop in the opposite direction. Filled with remorse over her role in King Duncan's murder, which has since led to a series of other bloody crimes, Lady Macbeth loses her sanity and, ultimately, her life (presumably by suicide).