Leukopenia is an infrequently recognized complication of penicillin-related antibiotic and cephalosporin therapy. We describe our experience with nine individuals and reviewed reports of 11 cases from the literature. Seventy-six percent of cases occurred in individuals receiving 150 mg/kg/day or more of the various penicillin and cephalosporin homologues; 67% received these high doses for two or more weeks before the onset of leukopenia. Leukopenia was unusual within the first week of antibiotic treatment. Standard medical texts often recommend blind administration with 12 to 23 g/day of these antibiotics regardless of weight. It is suggested that these antibiotics be administered according to a maximum milligram per kilogram per day dosage as is done in children. Beyond the first week of administration, careful monitoring of the blood cell count should be conducted for those receiving high doses of these antibiotics.