Abstract Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6 mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4 12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h. The mean maximal serum drug concentration (mean C_max) of MTX attained at 1 2 h after ingestion of the first capsule was 0.215 and 0.252 μM, respectively, in the first and the follow-up week. The mean C_max after ingestion of the third capsule was 0.223 μM and 0.357 μM. The mean C_max of 7-OH MTX was 0.0334 and 0.0289 μM for the first capsule, and 0.0495 and 0.0672 μM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6 mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5 mg per week.