The effects of halothane anesthesia and cyclopropane anesthesia on vascular smooth muscle and reflex adjustments of peripheral vascular resistance were studied in the isolated innervated dog gracilis muscle cross-perfused with donor blood. Administration of halothane (1.5%) or cyclopropane (35%) to the donor animal resulted in vasoconstriction in the gracilis muscle. Vasoconstrictor responses to local injection of norepinephrine were unchanged by cyclopropane and depressed significantly by halothane. Vascular resistance in the muscle was not altered by administration of halothane or cyclopropane to the recipient animal. Reflex vasoconstriction was depressed by halothane and by cyclopropane in the recipient animal, whereas reflex vasodilatation was unaffected by either agent. We conclude that both depression of vascular responsiveness to norepinephrine and interference with reflex vasoconstriction contribute to the hypotension ordinarily observed with halothane anesthesia. No evidence was found for activation of the sympathetic nervous system or sensitization of vascular smooth muscle to norepinephrine by cyclopropane. The maintenance or slight elevation of blood pressure observed with cyclopropane anesthesia may well be related to the direct vascular smooth muscle-stimulating activity of this agent.