Although hemorrhage severely depresses macrophage functions, it is not known whether the increased TNF-α or PGE2 production is responsible for it. To study this C3H/HeN mice were bled to mean blood pressure of 35 mmHg for 60 minutes, resuscitated, and treated with either ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage increased plasma prostaglandin E2 (PGE2) levels by 151.7% ± 40.0% (p < 0.05) and significantly decreased peritoneal macrophage (pMø) antigen presentation (AP) by 60.5% ± 7.3%, Ia expression by 52.3% ± 7.6%, and interleukin-1 (IL-1) synthesis by 60.5% ± 12.3% compared to shams. However ibuprofen treatment reduced PGE2 plasma levels by 61.3% ± 12.1% and significantly increased AP (+237.0% ± 95.3%), Ia expression (+72.8% ± 27.5%), IL-1 synthesis (+235.7% ± 134.7%), and cachectin synthesis (+485.8% ± 209.0%) compared to vehicle-treated animals. These results indicate that prostaglandins but not cachectin are involved in the suppression of pMø functions following hemorrhage because blockade of prostaglandin synthesis improved depressed macrophage functions despite enhanced cachectin synthesis.