Chlorambucil, an oral alkylating agent, was administered for a total of 205 courses to 126 patients with lymphoma or chronic lymphocytic leukemia. The drug benefited three fourths of the patients with Hodgkin's disease and one half of the patients with leukemia or small cell lymphosarcoma. Only one of 12 patients with reticulum cell sarcoma responded. The gradual appearance of marrow depression was the only important toxicity of the drug. Responsiveness to the drug was well maintained during subsequent chlorambucil treatments, while initially unresponsive patients, with but one exception, did not respond to later trials of the drug. The combined treatment of corticosteroids and chlorambucil in a small group of anemic and thrombocytopenic patients with leukemia may have allowed the administration of an effective dose of the alkylating agent, but did not enhance its therapeutic effectiveness.