Nabumetone is a novel nonsteroidal antiinflammatory drug (NSAID) with a unique pharmacologic profile. It is nonacidic and demonstrates minimal prostaglandin synthesis inhibition. Because it is nonacidic, nabumetone cannot dissociate in the stomach after oral administration. In contrast, acidic NSAID (active cyclooxygenase inhibitors) can dissociate and concentrate by "ion trapping" in the gastric mucosa, inhibit prostaglandin synthesis and, therefore, cause topically induced erosive mucosal damage. After absorption, nabumetone is converted by first pass metabolism to the active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA), an effective inhibitor of prostaglandin synthesis. 6MNA is hepatically, not renally, cleared and differs from other NSAID because it does not undergo enterohepatic circulation in animals or man. This is thought to contribute to its apparent lack of severe gastrointestinal irritancy. The pharmacologic profile of nabumetone can be summarized in terms of the very large "therapeutic ratio" in comparison with other NSAID.