Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used to treat arthritis, menstrual pain, and headache. Although they are effective, their long-term use is limited by gastrointestinal effects such as dyspepsia and abdominal pain and, less often, gastric or duodenal perforation or bleeding. Development of the coxibs, a new group of antiinflammatory drugs, represents a response to the unsatisfactory therapeutic profile of NSAIDs. Both groups of drugs inhibit prostaglandin G/H synthase, the enzyme that catalyzes the transformation of arachidonic acid to a range of lipid mediators, termed prostaglandins and thromboxanes (Figure 1). However, whereas NSAIDs inhibit the two recognized forms of the . . .