We have shown that prophylactic treatment with a high dose of corticosteroid stabilizes the cardiovascular system, prevents hemorrhage of the small intestine, and improves survival. In this study we evaluated the effect of corticosteroid administered early after the manifestation of shock induced by endotoxin on blood pressure, heart rate, respiration rate, hematocrit, blood glucose, acid-base parameters, small-intestinal hemorrhage, and survival in the conscious rat. Male Sprague-Dawley rats were anesthetized with 2% enflurane and cannulae were placed in the carotid artery and jugular vein. Following recovery the animals were challenged with endotoxin (20 mg/kg). After the mean blood pressure had fallen to below 70 mm Hg the animals received corticosteroid (300 mg/kg) or an equivalent volume of saline. Supplemental doses of 30 mg/kg were given 90 min and 180 min after the initial dose. In groups other than those dealing with survival, rats were sacrificed after 4 h for pathological examination. When endotoxin was administered to untreated animals, 0/10 were alive at 15 h. In the treated group, 6/10 were alive at 24 h. Treatment shortened the early hypotensive period, but resulted in lower blood pressure from + 60 min to sacrifice. Heart rates in the treated animals were lower, pulse pressures were higher, and respiration rates were the same. Corticosteroid treatment prevented hypoglycemia, hemoconcentration, and acidemia, and markedly inhibited hemorrhage of the small intestine. Large-dose corticosteroid treatment is highly effective even when administered after the first evidence of shock induced by endotoxin in the conscious rat.