Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 +/- 19 months (mean +/- SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 +/- 1.2 to 2.7 +/- 3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use.