Forty-one patients with rheumatoid arthritis (RA) were treated with a weekly low-dose of methotrexate for a mean period of 32 months (range, 5-81 months) and were given a mean total dose of 954 mg (range, 145-2000 mg). Eighty-three percent of the patients improved. Of these 39% (16 patients) had a complete clinical remission and 17% (7 patients) showed marked improvement, 27% (11 patients) showed moderate improvement and 17% (7 patients) were unchanged. Patients responding to methotrexate therapy maintained the improvement as long as the therapy continued, unless severe infections occurred. Seven patients withdrew during the study including two, who died of myocardial infarction. Methotrexate was withdrawn because of adverse drug reactions in two patients, fear of toxicity in two and for administrative reasons in one patient. Adverse reactions developed in 25 patients (61%). In all but two cases these reactions were mild and reversible. Pancytopenia, a major side effect, was present in two patients: in one patient in association with pneumonia and in the other patient associated with an acute infectious enteritis (after three years treatment in the first and six years in the second patient); both recovered when methotrexate was discontinued. Age, sex, duration of treatment did not remarkably influence the outcome of therapy or the occurrence of adverse reactions.