The incidence, severity, and management of diarrhea during longterm administration of auranofin (AF)--up to 33 months--were evaluated prospectively in 137 patients with active rheumatoid arthritis. At least 1 episode of diarrhea was reported in 101 patients (74%), but the rate of occurrence/patient-months of therapy was 24% (569 events/2,370 patient-months of treatment). The monthly prevalence declined from a range of 30-40% during the initial 6 months to about 10% for patients treated for 18-24 months. Most diarrhea was intermittent and mild; only 11 patients (8%) discontinued treatment because of diarrheal symptoms. No intervention was required in 46 of the 101 patients affected. In 44 others, loose stools were successfully managed with antidiarrheal medications, a reduction in dosage, or both. Although diarrhea is a common event during AF administration, particularly early in therapy, for most patients it usually does not significantly interfere with treatment.