The case of a patient who developed Hodgkin's disease three years after commencement of therapy with phenytoin is presented. Humoral and cellular immunological capacity were significantly depressed. Phenytoin caused a striking increase in DNA synthesis when lymphocytes were culture in the presence of this drug, in contrast to significant inhibition in the lymphocytes of control subjects. These findings are consistent with the hypothesis that both chronic antigenic stimulation and immunosuppression by phenytoin and involved in the induction of lymphoma.