Splenectomized patients are at risk of overwhelming infection and are advised to take life-long prophylactic oral penicillin. Compliance studies have not been published for adults in this situation. We used a standard biological assay to detect penicillin in the urine of 58 splenectomized patients. 24 (42%) patients had evidence of penicillin in their urine. Patients' sex, age, years from splenectomy and underlying diagnosis were not important factors in identifying good or poor compliance. Since 58% of patients did not take their penicillin on the day studied, we need to consider alternative strategies of antibiotic use and patient education.