Previous studies of sulphasalazine in rheumatoid arthritis have chosen an empirical dose based upon its use in ulcerative colitis. In this study we compare the efficacy and toxicity of two doses (1.5 g/day and 3 g/day, 30 patients per group), and attempt to relate efficacy to serum levels of sulphasalazine and its metabolites. After six months 24 of the low-dose group and 20 of the high-dose group remained on treatment. Greater improvement was seen in the high-dose group. When dose was expressed as mg/kg, the dose efficacy ratio became more apparent and a dose of greater than 40 mg/kg/day appears to confer greater benefit. No relationship was demonstrated between serum levels of sulphasalazine or its measured metabolites, and efficacy. We conclude that response to sulphasalazine in rheumatoid arthritis is dose dependent but does not relate to serum levels of sulphasalazine, sulphapyridine, or acetyl sulphapyridine.