Serum concentrations of methotrexate (MTX) were compared in 20 patients after administration of 15 mg/m2 MTX orally, intramuscularly, orally in divided doses, and/or intravenously. Higher and more sustained concentrations usually occurred 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.