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1. What's going on? What's happening? So, what's up with Terry? He seems off lately. Well, what's up? Why are you so upset with me?
2. How are you? How are things? (Used as a greeting that doesn't require an answer.) Hey, Tom, what's up? Long time no see! A: "Hi Sarah!" B: "What's up, Janet!"
See also: up
Inf. Hello. What is happening? What's up? How're you doing? Hey, Chuck! What's up?
1 what’s the matter?: What’s up with him? He looks furious.
2 (especially American English) what’s new?; what’s happening?: Hey Jo, what’s up?