Prostaglandin E1 and methylprednisolone sodium succinate were administered simultaneously after shock in an intact canine hemorrhagic shock model and compared to treatment with each agent singly and with a 60 cc saline infusion. A detrimental effect of the prostaglandin E1/steroid combination was evidenced by decreased heart rate, mean arterial and central venous pressures, cardiac output, and arterial pH, and increased venous lactate. Survival was poor after the combined regimen. These changes may be related to vasodilation in the peripheral vascular system, causing pooling of blood. Lysosomal membranes were stabilized in spite of prolonged hypoperfusion.