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Rheumatic diseases such as rheumatoid arthritis (RA) have an autoimmune basis, in which the body inappropriately makes antibodies that recognize and attack the body's own tissues. The efficacy and toxicity of two drugs, azathioprine (AZA) and methotrexate (MTX), were compared in 64 patients (43 female) with RA who were unresponsive or had suffered side effects from gold therapy or d-penicillamine. Of the 33 subjects taking AZA, 13 discontinued due to severe side effects, chiefly severe vomiting. MTX side effects were primarily consisted of elevated blood levels of liver enzymes (suggestive of liver dysfunction), mouth ulcers, nausea, and vomiting. Of the 50 patients (20 receiving AZA and 30 receiving MTX) who completed 24 weeks of drug therapy, patients using MTX improved significantly compared with baseline status, medical symptoms, and laboratory results. This improvement extended to 48 weeks of therapy. Assessments at monthly intervals up to 24 weeks showed significantly greater improvement with time in the number of swollen joints, level of pain, and laboratory tests indicating severity of inflammatory disease. Seventy-six percent of MTX patients and 50 percent of AZA patients had a significant improvement in the disease activity score after 48 weeks, but MTX patients responded more rapidly. Overall, the study indicates that, for treating RA, MTX is more effective and produces fewer severe side effects than AZA. (Consumer Summary produced by Reliance Medical Information, Inc.)