Multiple immunologic side effects have been ascribed to phenytoin. Numerous reports in the literature discuss the possible cellular and humoral abnormalities that appear to be present in patients given phenytoin. The most consistent finding is a reduction in serum IgA found in up to 20% of patients. To resolve some of the conflicting studies on cellular immune status, 191 patients taking phenytoin were evaluated initially with an serum IgA determination, and then further immune studies were done on the 11% with IgA values lower than two standard deviations below the mean. Data collected included total lymphocyte counts, lymphocyte population studies, and responses to in vitro mitogen stimulation. Only 2 of 191 patients had serum IgA values less than 5 mg/dL, which is an incidence not significantly different than that in the population at large. The patients with decreased serum IgA values did not have an increased incidence of autoimmune phenomena, allergic disorders, gastrointestinal manifestations, or recurrent upper respiratory tract infections. Their cellular immune status showed no significant variations from control values. Thus it appears that routine monitoring of patients on phenytoin with serum IgA determinations is of limited value, and the immunologic side effects of phenytoin are not expressed as a cellular abnormality.