Methylsulphasalazine, which differs from sulphasalazine by the addition of one methyl group, may provide the benefits of the parent drug with fewer side-effects in rheumatoid arthritis (RA). We describe the outcome of its use in RA. Of 21 patients entered into the study, 10 successfully completed 6 months of therapy; five developed adverse effects, four withdrew for reasons unrelated to drug treatment and two stopped because of inefficacy. No serious adverse effects were reported. A statistically significant improvement in most clinical assessments was observed from weeks 8-12 onwards. Significant improvement in plasma viscosity was observed and there was a trend towards improvement in serum CRP, histidine and IgM concentrations. There was a good correlation between mean serial changes in clinical and biochemical assessments indicating that the drug may exhibit the properties of a second-line agent. Median steady-state serum concentrations of methylsulphasalazine and methylsulphapyridine were 26.6 micrograms/ml and 2.85 micrograms/ml respectively.