This study was designed to evaluate 1) whether the initial compensatory skeletal muscle vascular constriction induced by hemorrhagic hypotension is primarily the result of increased adrenergic neural tone rather than circulating vasoconstrictor agents, and 2) whether the secondary skeletal muscle decompensatory vasodilation is caused by inhibitory action of prostaglandins on peripheral adrenergic nervous system. A constant-flow vascularly isolated double canine gracilis muscle preparation in which one muscle served as innervated control for the contralateral muscle was used. Dogs were subjected to standard stepwise hemorrhagic shock protocol. In series 1, perfusion pressures of control muscles were compared to denervated muscles with the result that innervated muscle perfusion pressures increased initially from 105 to 175 mmHg but subsequently fell significantly (P less than 0.05) to 147 mmHg. Only modest increases in perfusion pressures with no significant secondary fall were noted in denervated muscles. Series 2 compared innervated control perfusion pressures to pressures perfusing muscles pretreated with prostaglandin-synthesis inhibitor sodium meclofenamate (MCF). The MCF-treated muscle perfusion pressures rose to 260 mmHg where they remained without the secondary fall noted in control muscles. These data support the two hypotheses tested.