Postsplenectomy, 41 patients previously treated for Hodgkin's disease were given pneumococcal vaccine, and type-specific antibody levels were measured before and after immunization. Postimmunization antibody levels in patients with Hodgkin's disease were significantly lower than those in normal control subjects for 10 of the 12 serotypes measured. Mean postimmunization antibody level for patients (587 ± 427 ng of antibody nitrogen/mL) was much lower than that for control subjects (1787 ± 694). Antibody levels tended to increase with time from therapy for Hodgkin's disease, and several patients who had not received therapy for more than 3 years had normal responses to immunization. Despite vaccination, one patient developed pneumococcal meningitis and another, pneumococcal bacteremia. Both infected patients had low postimmunization mean antibody levels (282 and 137 ng/mL, respectively). Postsplenectomy sepsis in patients with Hodgkin's disease is related to a humoral immune deficiency probably induced by radiation and chemotherapy, and this immune deficiency persists for several years.