A series of novel 2,3-diaryl-2-cyclobuten-l-ones have been synthesized and have been evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1 and COX-2. 4,4-Dimethyl-2 phenyl-3-[4-(methylsulfonyl)phenyl]cyclobutenone 22 was found to be highly selective for inhibition of COX-2 and was orally active (EDs0 = 2.4 mg/kg) in the rat paw edema model.