The effects of prolonged bicuculline-induced seizures on cerebral blood flow and metabolism were determined in paralyzed, mechanically ventilated neonatal dogs. Transient changes occurring early in the course of status epilepticus included significant arterial hypertension, hypocarbia, elevation of plasma norepinephrine levels, and decline in brain glucose concentration. Cerebral blood flow remained elevated throughout the 45 minutes of seizure. Determination of cerebral metabolite values by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy and by in vitro enzymatic analysis of frozen brain samples showed significant decreases in the level of phosphocreatine and relatively less change in ATP values. Progressive intracellular acidosis occurred, coincident with elevation of brain lactate concentrations. We conclude that the physiological and metabolic alterations that occur during prolonged seizures are not uniform, but change with time. Any hypothesis advanced to explain the mechanism of neuronal injury during prolonged seizures must take into account these temporally related changes.