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8.
Originated in Philadelphia circa 1998. When discussing events that are of intrest to both parties. The person that didn't know what was going down would say that's what's up.
usally rhetorical.
Frank:Yo! There's a big concert at the spectrum tonite?
Jonny: that's what's up!
by HRM SMK April 02, 2008
 
9.
You for real?
Girl: I think we better off friends...
Guy: Thatz Whats Up?
by banginbootagurl May 26, 2004
 
10.
Something bad that happens
Thats whats up when you mess with me
by Dildo August 04, 2003