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1. I know you are, but what am I?
It's quite simply the most retarded comeback someone makes when they've completely lost the argument. This statement signifies that the argument has gone to a completely immature level. Below is a hardcore argument starting with the immature statement :)
Person 1: I know you are, but what am I?

Person 2: Good question. What are you?

Person 1: Wow, you're so dumb, you don't even know what I am?

Person 2: You're so dumb, you can't even answer my question.

Person 1: I don't answer stupid questions. Sorry.

Person 2: Then you shouldn't have made your first one.
2. I know you are, but what am I?
A retort with profound implications. Pee Wee's greatest contribution to youth culture.
Person A: You smell bad.

Person B: There's this thing about a small squirrel and how nobody loves you. Hi-ya! Now that's what I call a verbal bitch-slap.

Person A: I know you are, but what am I?

Person B: Haha what a complete fail of a a comeback. It's like, your face is all red, and you can't come up with a comeback.

Person A: It made no sense, but therein lies the point. The notion that one needs to respond with a rehearsed "comeback" is inane. Your squirrel-centric comeback was also inane; it failed to address your abhorrent smell, it seemed to mistake randomness for wit (really a squirrel?), and the mere fact that you would use it as an example of a verbal bitch-slap is laughable, as it lacks slap. It is quite slap-less. I respond to inanity with inanity.

Person B: Well, "your" still a faggot. And now I'm going to win this by blowing your mind with an ounce of inverse-Descartian drivel.

Person A: Nooooooooooooooo
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