We examined the role of prostanoids to bicuculline-induced seizures in newborn pigs. Using the closed cranial window method and radioimmunoassay for prostanoids, we found that pial arterioles dilated during seizures; this dilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) levels of prostaglandin E2, 6-ketoprostaglandin F1 alpha, prostaglandin F2 alpha, and thromboxane B2. Using radioactive microspheres, we found cerebral blood flow (CBF) increased dramatically during seizures in piglets. To examine the effects of pharmacological blockade of cyclooxygenase, we determined CBF in piglets pretreated with indomethacin (5 mg/kg) and in a corresponding group of piglets made hypothermic to be sure preseizure CBF values were similar. In the hypothermic group, CBF increased during seizure, but the increase in CBF during seizure in the indomethacin group was reduced dramatically in all brain areas. We conclude that 1) bicuculline-induced seizures result in pial arteriolar dilation and increased CBF; 2) CSF levels of prostanoids increase during seizures; and 3) pretreatment with indomethacin severely blunts increases in CBF during seizures.