Wegener granulomatosis was diagnosed in a 42-year-old woman in 1965. Although a regimen of azathioprine and prednisone was helpful, the disease progressed. Cyclophosphamide was added to this regimen in 1969. On three separate occasions her disease relapsed when cyclophosphamide therapy was discontinued. In 1984, she developed cyclophosphamide-resistant disease and drug toxicity. We were able to discontinue cyclophosphamide therapy after a trimethoprim-sulfamethoxazole regimen that was begun in February 1985 led to rapid improvement, a fall in the erythrocyte sedimentation rate, and a complete remission. Her 22-year survival is the longest one reported. Because patients with Wegener granulomatosis sometimes respond to trimethoprim-sulfamethoxazole, this therapy deserves careful study and implies that Wegener granulomatosis is an as yet unidentified infection.