A double blind trial comparing recominant interferon gamma (IFN gamma) with placebo in rheumatoid arthritis is presented. Twenty-six patients entered the study and 22 completed the 6-month period. IFN gamma was administered subcutaneously as was placebo; the 1st week, patients treated with the active compound received a daily subcutaneous injection of 100 micrograms of IFN gamma and for the following 23 weeks the schedule was decreased to 2 injections of 100 micrograms every week. No serious side effects were observed. After Week 24 the group treated with the active compound showed a significant decrease of the joint tenderness score and the placebo group showed a significant increase of the number of subcutaneous nodules. All other variables shifted in favour of the active compound but not significantly. More double blind trials with a larger number of patients and using other treatment schedules or other routes of administration are required.