Both clinical and laboratory studies are being undertaken to investigate the deleterious neurologic and developmental effects associated with cardiopulmonary bypass, hypothermia, and circulatory arrest in the neonate and infant. A prospective, randomized clinical study of 171 neonates and young infants compared circulatory arrest with low-flow bypass (50 mL.kg(-1). min(-1)). Circulatory arrest was associated with a higher incidence of early postoperative seizures as well as greater release of creatine kinase-BB. There was a strong correlation between duration of circulatory arrest and seizures (p=0.004). The late consequences of these findings will be known at the completion of developmental assessment of all patients at 1 and 4 years of age. Laboratory studies have used a miniature piglet model that closely replicates clinical circulatory arrest. High-energy phosphate stores determined by magnetic resonance spectroscopy were maintained in animals undergoing 1 hour of low-flow bypass but became undetectable after 32 minutes of a 1-hour period of circulatory arrest. However, they returned to baseline within 3 hours of reperfusion as did cerebral blood flow and metabolism determined by microsphere studies. Piglets undergoing 1 hour of circulatory arrest showed more rapid recovery of cerebral adenosine triphosphate content and intracellular pH when managed with the pH-stat strategy during hypothermic bypass than with the more alkaline alpha-stat strategy. Other laboratory studies have examined pharmacologic methods of reducing cerebral injury associated with circulatory arrest including aprotinin, anti-CD18, neuronal receptor antagonists (MK801, NBQX), and blockade of glutamate release with adenosine in a cerebroplegia solution. These studies have suggested a number of promising approaches to improving the technique of circulatory arrest.