Serum concentrations of methotrexate (MTX) were compared in 20 patients after administration of 15 mg/mz MTX orally, intramuscularly, orally in divided doses, and/or intravenously. Higher and more sustained concentrations usually occurfed after intramuscular administration of the drug. Approximately 50% of the patients had measurable serum concentrations 24 hours after a dose, except when the drug was given intravenously. In patients continued on MTX twice a week, antimetabolic effects appeared sooner in persons with more sustained serum levels. CUMW 36: 1619-1624, 1975. VlDENCE CONTINUES TO ACCUMULATE IN E the literature demonstrating that the duration of the time that methotrexate (MTX) is present in the blood stream is an important factor in the development of the drug's an-timetabolic effect^.^^^^'^^'^^'-^^ A dose of 94 mg/lcg in mice in a single intraperitoneal dose will produce antimetabolic effects equivalent to that of 9.4 mg/kg when the dose is divided and given in five parts.' In humans, a dose of 25 mg given intravenously daily for 5 days produces antimetabolic effects equivalent to those of a 5-mg dose per day when administered by a 24-hour infusion over a 4-6-day period." Livingston and Carter" detail the wide variety of antitumor responses that have been obtained with M T X in the past, the best therapeutic results in selected tumors occurring in patients in whom the drug was given in such a way as to maintain a prolonged and relatively steady blood level of circulating drug. This has raised the question of what is the most practical way to administer this drug to maintain a blood level for a significant period of time in patients with solid tumors. Previous pharmacokinetic studies have shown that small doses of MTX are absorbed and ex
