The effects of steriodal and nonsteroidal antiinflammatory agents on mortality, plasma glucose and lactate levels, and pathologic alterations associated with Escherichia coli endotoxemia were assessed in neonatal rats. Animals were first injected subcutaneously with either high (LD95) or moderate (LD35) doses of endotoxin and immediately thereafter were administered either saline, dexamethasone, indomethacin, or glucose. Animals treated with saline or glucose developed significant hypoglycemia and hyperlactacidemia. Dexamethasone and indomethacin ameliorated the fall in glucose and the rise in lactate during high dose but not moderate dose endotoxemia. Pathologic changes consisting of widespread inflammation and hepatic necrosis were most marked in the saline- and indomethacin-treated animals. Only dexamethasone significantly reduced mortality at either LD95 or LD35 doses of endotoxin. We conclude that dexamethasone may reduce mortality in endotoxic shock through mechanisms other than simple amelioration of changes in plasma glucose.