A murine model was used to test the effects of various therapeutic modalities on the rate of death following intra-abdominal sepsis as produced by cecal ligation and puncture (CLP). There were no deaths among sham-operated control mice after ether anesthesia, whereas CLP produced a mortality rate of 100% by 24 hours. When CLP was followed at 16 hours by excision of the cecum and saline peritoneal lavage (CLPE), the mortality rate was 20% at 24 hours and 60% at 72 hours. The therapeutic modalities consisted of gentamicin (1.5 mg/kg) alone or in combination with methylprednisolone (50 mg/kg) or tuftsin (1 mg/kg) administered before CLP and at 16 and 24 hours after CLP. Separate groups of animals also received only methylprednisolone or tuftsin, a tetrapeptide produced by the spleen. Compared with the mortality rate in the CLPE group, mortality at 24 and 72 hours was decreased for gentamicin alone (0% and 10%, respectively), tuftsin alone (10%, 40%), or the two in combination (0%, 20%). As compared with CLPE, methylprednisolone led to increased mortality rates at 24 and 72 hours (70%, 80%). The data (significant at P less than 0.01, X2 analysis) suggest that gentamicin and tuftsin may improve the rate of early survival after intra-abdominal sepsis in this Model. Steroids do not seem to be beneficial and may, in fact, be harmful.