Thirty-six patients with severe, debilitating, and refractory psoriasis, arthritis, or both were treated with parenteral methotrexate for periods of time that varied from six months to three years. Five of the 36 patients had previously received oral methotrexate without adequate control of the disease. Of the patients, 80% responded to 25 and 50 mg of the drug biweekly. The remaining 20% could be controlled with 75 mg biweekly, however, the incidence of drug-induced toxicity increased significantly with the higher drug dosages, but was not severe enough to cause permanent cessation of therapy. Data obtained were compared with data presented by other investigators using the oral and parenteral routes. The regimen of 25 to 50 mg of biweekly parenteral methotrexate gave therapeutic results comparable to those reported by others using higher parenteral and daily oral dosages. Knowledge of the pharmacology of methotrexate leads one to believe that the use of this regimen will reduce the potential for long-term toxicity.