We reviewed the literature on 7 investigational nonsteroidal antiinflammatory drugs (NSAIDs): fenbufen, flurbiprofen, tiaprofenic acid, diclofenac, fenclofenac, etodolac and proquazone. These drugs all appear to be at least as effective as currently marketed NSAIDs. Toxicity reported with these newer agents is similar to that seen with other drugs in this class, with gastrointestinal complaints being most commonly reported. The frequency of gastritis and the extent of gastrointestinal microbleeding are less than what occur with aspirin therapy. Fenclofenac may affect thyroid function tests, an effect not noted with other NSAIDs. Proquazone and fenclofenac may have some effect on immunologic function similar to those of slow-acting antirheumatic drugs. These drugs decrease immunoglobulins, rheumatoid factor and C-reactive protein. The place for these drugs in the management of rheumatic diseases has yet to be defined. They may prove to be more beneficial than currently marketed drugs for some patients.