Traumatic and thermal injuries are leading causes of mortality and morbidity due to their high incidence of infection. Host defense is vital to recovery in these patients yet incompletely understood. On days 1, 7, and 14, serum immunoglobulins of the IgA, IgG, and IgM classes were measured in 46 consecutive patients who sustained severe trauma with an injury severity score of at least 20. The patients were divided into four groups: 1) an uneventful recovery group (n = 11) of nonthermal trauma patients who did not become infected; 2) an infected nonthermal group without splenectomy; 3) an infected group of burn patients; and 4) 12 patients who underwent splenectomy of which nine became infected following nonthermal trauma. In each patient group, IgA, IgG, and IgM were all reduced, and group 1 had a steady return to normal range. Group 2 patients exhibited supranormal responses in all 3 classes at one week and supranormal IgA and IgG responses at two weeks. In contrast, both infected burn and splenectomized patients had markedly reduced IgG and IgM levels compared with the group 2 patients (P less than 0.05). Splenectomy sharply reduced IgM response to infection at 7 and 14 days compared with nonsplenectomized infected posttraumatic patients. Immunoglobulin response after trauma depended on the type of injury, presence of infection, splenic function, and type of immunoglobulin. Recognition of immunoglobulin deficiencies in both the burn and splenectomized patient may permit focused therapy, such as specific replacement of these proteins.