A review has been conducted of ongoing clinical and laboratory studies of hypothermic circulatory arrest (HCA) and low-flow cardiopulmonary bypass (LFB) at a children's hospital in Boston. A prospective randomized clinical trial of HCA versus LFB has shown a higher incidence of perioperative seizures in patients randomized to HCA. At 1 year of age, neurologic and developmental studies have shown an association between seizures and worse outcome. Longer duration of HCA is associated with a worse score on the Bayley scale assessment of gross and fine motor function in particular, as well as a higher probability of neurologic abnormality. A retrospective review of development after HCA for Senning procedure has shown a correlation between more alkaline pH (alpha-stat strategy) during cooling before HCA and lower developmental score relative to a more acidotic strategy (pH stat). The institutional change to alpha-stat was accompanied by several cases of choreoathetosis after HCA. Currently, patients are being randomized between alpha-stat and pH-stat. Laboratory studies have used a piglet model with assessment of cerebral blood flow and metabolism as well as high-energy phosphates and cerebral pH determined by magnetic resonance spectroscopy. High-energy phosphates are maintained by a flow rate of 50 mL/kg/min but are undetectable after approximately 35 minutes of HCS. A pH-stat is associated with more rapid recovery of high-energy phosphates after HCA than alpha-stat. Recent studies have examined the role of nitric oxide in the causation of brain injury after HCA as well as the potential utility of cerebroplegia in increasing the safe duration of circulatory arrest.