The pharmacokinetics of moderate doses of methotrexate administered via the hepatic artery were studied in ten patients with cancer metastatic to the liver. Intra-arterial methotrexate showed two-compartment characteristics with a clearance of 79 ml/min/m2 and an apparent volume of distribution of 21.2 l/m2 body surface area. The average half-life of the early phase was 1.9 h and the terminal half-life was 14.4 h. The data were not different from those observed in similar patients after IV administration of equivalent doses of methotrexate.