Pyrimethamine, a substituted pyrimidine with potent folate antagonistic properties, was given orally to treat two episodes of meningeal leukemia in a longterm survivor with acute myeloblastic leukemia. Remissions of seven and at least 6 mo duration were obtained on the two occasions. Spinal fluid concentrations of pyrimethamine were 10-25% of the simultaneous plasma concentrations. Considerations regarding lipid solubility, body distribution, and easily reversible toxicity of pyrimethamine suggest that further therapeutic trials are warranted, especially in childhood lymphoblastic leukemia.