Methodology: All patients will be recruited from outpatient academic, private practice, and VA rheumatology clinics. Subjects will be between the ages of 19 and 80 years. No pediatric subjects will be enrolled. No enrollment restrictions are based on race, ethnic origin or gender. Inclusion criteria includes: formal diagnosis of rheumatoid arthritis per ACR criteria; disease duration of >6 months; at least 6 swollen and 6 tender joints on examination; and negative urine pregnancy test for premenopausal females. Specific exclusion criteria includes: previous treatment with leflunomide or combination DMARDs; abnormal lab values; history of allergy to sulfa, aspirin or tartrazine; any significant comorbid diseases; and unwillingness to avoid alcohol. Study subjects will return for evaluations every 8 weeks. All patients will be monitored for efficacy and signs of drug toxicity throughout the study by laboratory examination (CBC with platelets, AST or ALT, albumin, creatinine, and erythrocyte sedimentation rate), hand x-rays, retinal examination, and chest x-rays (if indicated). Every six months subjects will be asked to complete the ClinHAQ and SF36 questionnaires, designed to evaluate the effect of RA on daily live (ADLs). Subjects will be withdrawn from the study: due to pregnancy; serious adverse event not alleviated by symptomatic treatment; recurrent toxicity that reappears after treatment or drug suspension; lack of efficacy (20% improvement by week 32); non-compliance with the protocol; or withdrawal of consent. The primary study outcome measures were planned before data collection began.