Perinatal asphyxia is associated with an increased risk of cerebral palsy and significant mortality. We investigated the use of flunarizine, a calcium antagonist and MK-801, an excitatory amino acid antagonist, in preventing the sequelae of severe hypoxic/ischemic insults. Flunarizine was neuroprotective in the infant rat subjected to unilateral carotid ligation and 2 h of hypoxia. Preliminary analysis of experiments in a novel model of cerebral ischemia in the fetal sheep suggests that prophylactic treatment with flunarizine greatly modified the outcome after 30 min of total ischemia. Treatment with MK-801 prevented post-ischemic seizures. The background to these developments is outlined and future prospects considered.