A series of novel 2, 3-diaryl-2-cyclobuten-1-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 (ED50= 2.4 mg/kg) in the rat paw edema model.