Eighty patients with active rheumatoid arthritis (RA) entered a double-blind randomized study of 24 weeks duration, to compare the efficacy and toxicity of hydroxychloroquine, dapsone, and a combination of both drugs in treatment of RA. Evaluation of changes in clinical, laboratory and radiologic variables was based on 63 patients completing the trial. There was no clear difference between the three therapy groups in most inflammatory variables after 24 weeks. However, only patients receiving the combination therapy improved significantly in all clinical and laboratory variables. Nine patients in the combination group and four in each single drug group discontinued during the trial, mainly because of toxicity. Four patients taking the combination therapy withdrew because of hemolytic anemia, and none in the dapsone group. These findings suggest that hydroxychloroquine in combination with dapsone is somewhat more effective and less tolerated than single drug treatments.