BACKGROUND AND PURPOSE Juvenile rheumatoid arthritis (JRA) can result in disability, growth disturbance, and systemic complications. This study investigated the efficacy and adverse effects of azathioprine (AZA) therapy in children with JRA. METHODS Data from the medical records of 24 children with JRA treated with oral AZA during the period from 1988 to 1998 were retrospectively analyzed. All 24 patients had received two or more nonsteroidal anti-inflammatory drugs (NSAIDs) and 12 had received disease-modifying antirheumatic drugs (DMARDs) prior to the start of AZA. Of the 24 patients, 21 were corticosteroid-dependent prior to the onset of AZA therapy. The indication for AZA therapy was lack of efficacy of the current treatment regimen. The initial and maximal doses of AZA averaged 1.7 mg.kg-1.d-1 (range, 1-3 mg. kg-1.d-1) and 1.9 mg.kg-1.d-1 (range, 1-6 mg.kg-1.d-1), respectively. The mean duration of treatment was 13 months (range, 4-37 mo). The mean duration of follow-up was 45 months (range, 7-137 mo) from the start of AZA therapy. RESULTS Fifteen children (62.5%) showed clinical improvement, while the other nine (37.5%) achieved clinical remission. AZA treatment resulted in a more than 50% reduction in the required corticosteroid dose in seven children and complete discontinuation of corticosteroid administration in eight children. None of the patients treated with AZA doses of 1 to 3 mg.kg-1.d-1 developed AZA-related side-effects. Two patients suffered from AZA-related adverse effects due to AZA overdose (6 mg.kg-1.d-1). Both experienced pancytopenia and disseminated infection, which resolved following reduction of the AZA dose to 3 mg.kg-1.d-1. CONCLUSIONS AZA is an effective and well-tolerated steroid-sparing agent for JRA refractory to NSAIDs or DMARDs.