We examined effects of indomethacin, meclofenamate, and prostaglandin E1 on systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance of anesthetized juvenile goats in severe hemorrhagic shock. Hemorrhagic shock was characterized by low systemic arterial pressure, decreased vascular resistance, and reduction in cardiac output. In acute experiments, indomethacin (3.4 mg/kg) attenuated the systemic hypotension of hemorrhagic shock. The increase in systemic arterial pressure following treatment with indomethacin was the result of increased systemic vascular resistance. Systemic arterial pressure, heart rate, and cardiac output fell during intravenous prostaglandin E1 infusions (3 micrograms/kg/min for 5 min) in both controls and goats in shock. The effects of prostaglandin E1 were more pronounced and prolonged in goats that had undergone the hemorrhagic-shock-producing procedure followed by indomethacin than in control animals treated with indomethacin but not hemorrhaged. Not only was meclofenamate less effective than indomethacin in increasing the systemic arterial pressures of goats in this type of hemorrhagic shock, but also it attenuated the pressor effects of indomethacin. Substances synthesized via prostaglandin fatty acid cyclo-oxygenase may be involved in the systemic hypotension that is characteristic of hemorrhagic shock.