Ninety-two patients with intractable rheumatoid arthritis (RA) participated in an open prospective study of the longterm efficacy and toxicity of methotrexate (MTX), administered orally at a constant dosage of 7.5 mg/week. Twenty-four patients (25%) had to be withdrawn from the study within the first 12 months because of inefficacy or adverse reactions with a fatal outcome in 2 patients. In the remaining 68 patients, the mean duration of therapy was 19 months. Sixty-three of 92 patients (68%) experienced significant clinical improvement after one year, 23 (25%) were in clinical remission. Twenty-three of these patients initially responded well but relapsed after a median of 15 months of therapy. In 5 patients (5%) the disease activity remained status quo. Toxicity was noted at some time in 51 patients (54%), consisting of clinical side effects in 37 patients (40%) and biological abnormalities in 36 patients (39%), including 9 patients (10%) with blood and bone marrow toxicity, in whom renal function at start was normal. Two of these latter 9 patients had a fatal outcome because of an unexpected renal deterioration due to intercurrent disease. Thus, MTX at this constant low dose appears to be a temporarily valuable therapy for intractable RA. Careful monitoring is necessary in view of the potentially dangerous side effects.