The plasma concentration and urinary excretion of methotrexate were followed in twelve psoriatic patients after intravenous and oral doses of methotrexate ranging from 7.5 to 30 mg. In six of the patients, a nonlinear relation was found between the fractional amount of methotrexate excreted in the urine and the corresponding area under the plasma concentration-time curve. The methotrexate clearance was found to be increased during the initial high plasma concentration, probably due to saturation of the tubular reabsorption of methotrexate. Considerable interindividual variation was found in the apparent saturation point of the active reabsorption, but up to 500-800 ng/ml first order kinetics still applied. At plasma concentrations below saturation, the renal clearance of methotrexate ranged from 52-102 ml/min (mean +/- SD, 83 +/- 19.4 ml/min).