Treatment records of 1800 patients with rheumatoid arthritis who were included in the clinical trials of auranofin in the United States were examined for data on development of proteinuria. Three percent (41) of 1283 auranofin-treated patients had an abnormal 24-hour urine protein level: 15 had mild (0.15 to 1 g/d), 17 had moderate (1 to 3.5 g/d), and 9 had heavy (greater than 3.5 g/d) proteinuria. Permanent renal impairment did not occur, and proteinuria did not persist beyond 12 months in most patients. Seven of eight patients who were rechallenged when the proteinuria had cleared were able to continue treatment without relapse. No clinically discernible risk factors were found. Biopsy specimens from 4 patients showed membranous glomerulonephritis, which indicates an underlying immunopathologic mechanism. In similar groups of patients, the risk of developing proteinuria with auranofin therapy is significantly less than that with parenteral gold therapy (p less than 0.05) and similar to that with background therapy with nonsteroidal antiinflammatory drugs (p = 0.92). The lower incidence and relatively benign nature of proteinuria seen in this review support previous findings that auranofin is better tolerated than injectable gold.