Whether Macbeth or his wife is more ambitious for him to become king is a perennial subject of debate. She is certainly aware that any ambitions she has can only be realized through him.

Questions of gender bending have arisen earlier in the play in connection with the witches, who to Banquo’s eyes seem both female and male. This implies that power invested in women is supernatural or unnatural. Lady Macbeth’s request or demand, “Unsex me…,” suggests that she identifies being female with weakness, and this desire may make her seem unnatural or witchlike.

By late in Act I, Macbeth has made great advances with his plan. In line with one of the witches’ predictions, he has been made Thane of Cawdor. He writes this, and of the other part of the prophecy—that he will be king—in a letter to his wife, which she is reading at Scene 5’s opening, while she is alone on stage. Her husband encourages her to rejoice and mentions the “greatness that is promised thee.”

Talking to herself, her response to the letter is oddly critical. Rather than “rejoice,” she immediately worries about her husband’s weakness, as his “nature… is too full o' the milk of human kindness….” She speaks of the “illness” and need to “play false” that will be required for him to win but that she thinks he lacks.

After speaking with the messenger who arrives, she calls upon three related forces: spirits, ministers, and night. To each in turn, she directs a request or command.

Come, you spirits

That tend on mortal thoughts, unsex me here,

And fill me from the crown to the toe top-full

Of direst cruelty! make thick my blood;

Stop up the access and passage to remorse,

That no compunctious visitings of nature

Shake my fell purpose, nor keep peace between

The effect and it! Come to my woman's breasts,

And take my milk for gall, you murdering ministers….

The changes to her female nature referred to in “unsex me” include thickening the blood and turning her breast milk to gall. She wants nothing natural to get in the way of her plan– “no compunctious visitings of nature/Shake my fell purpose”

Lady Macbeth clearly considers some of the negative consequences. She directs the spirits to give her “direst cruelty,” and knows that she must not afterward feel “remorse.” She also mentions that the killing should be done in the dark of night, associating deed and time with evil, “the dunnest smoke of hell”

Later it turns out that feeling normal human emotions is not really the problem she has to deal with, rather, her mind snaps.

First she calls upon them to unsex her.  As a women, she feels vulnerable and although she may want to kill the king and thus make her husband the new king, she doesn't feel that she is strong enough.

She asks them to empty her of all tender emotions and fill her up instead with direst cruelty.  She asks them to shield her against feeling remorse.

She asks them the keep her focused on her "fell purpose" and let nothing get in the way.  Her fell purpose, of course, is the death of Duncan.

Instead of the nurturing milk of a mother, she asks that they fill her breast with poison.

In other words, she asks them to give her the strength she feels that she needs to push her husband into killing the king and helping, if necessary.   She knows that as a women, her feminine sensibilities would interfere.  She feels that only the forces of evil can help her.

Reality is something else entirely as she later learns.