Asplenic patients are at increased risk for life-threatening infections with polysaccharide-encapsulated organisms, and reports of responses to polysaccharide vaccines have been conflicting. Thirty-six asplenic patients and 15 healthy controls were immunized with pneumococcal, Haemophilus influenzae type b (Hib), and meningococcal vaccines. Antibody concentrations to Hib and pneumococcal serotypes 14 and 18C were measured by ELISA. IgG antibody responses to all three antigens were similar in asplenic patients and controls at 28 days following immunization. In contrast, asplenic patients had significantly lower IgM concentrations in response to Hib (P<.05) and to both pneumococcal serotypes 14 (P<. 005) and 18C (P<.001). IgA anti-Hib antibody was also lower in the asplenic group, as was total anti-Hib antibody measured by RIA. These results document that IgG responses to polysaccharide vaccines are normal in asplenic patients. The impaired IgM responses of these patients may explain conflicting reports from studies that measured only total antibody-binding concentrations.