To test whether azathioprine in effective in rheumatoid arthritis in doses smaller than those normally used the drug was tested at 2 dosage levels, 2.5 and 1.25 mg/kg/day (2.5 AZ and 1.25 AZ), against placebo under double-blind conditions over 24 weeks. Dropouts were 7 out of 15 in the 2.5 AZ group, 4 out of 14 in the 1.25 AZ group, and 2 out of 13 in the placebo group. Some significant improvement occurred in all 3 groups, including those on placebo. However, the 2.5 AZ group fared significantly better than the placebo group, while the 1.25 AZ group results tended to fall between the other 2 groups. We conclude that, in order to obtain the reported effectiveness of azathioprine in rheumatoid arthritis, it is necessary to start treatment with 2.5 mg/kg/day. Halving this dosage reduces the effectiveness of the drug.