Gammahydroxybutyric acid has been proposed as an alternative to high-dose barbiturate therapy for protecting the brain after ischemic or traumatic insult. The cerebral and systemic metabolic and vascular effects of gammahydroxybutyrate and its lactone analogue, gammabutyrolactone, are addressed in this paper. In anesthetized normal dogs, gammahydroxybutyrate or gammabutyrolactone was infused intravenously at a rate of 1 gm/kg/hr. Cerebral blood flow (CBF) decreased progressively with increasing doses of either agent. Cerebral metabolic rate of oxygen (CMRO2) increased initially with gammahydroxybutyrate, but not following gammabutyrolactone. Reduction in CBF exceeded that of CMRO2 at all doses in both series. The primary systemic effect noted was a severe, lethal metabolic acidosis resulting from infusion of gammabutyrolactone. Gammahydroxybutyrate did not cause a similar acidosis. The imbalance of the CBG-CMRO2 reduction following gammahydroxybutyrate administration suggests that it has no advantage over barbiturates in the management of patients with cerebral vascular insufficiency or intracranial hypertension.