The mechanisms underlying cerebral vasodilatation during hypercapnia are not fully understood. To examine the role of nerves and prostaglandins in the regulation of basal blood flow and in hypercapnia-induced vasodilatation in the cerebral blood vessels of rabbit.Cerebral blood flow was measured by laser Doppler flow-meter in 18 NZW rabbits anesthetized with sodium pentobarbital. Tetrodetoxin was administered locally and indomethacin (a prostaglandin inhibitor) both locally and systemically before and during induction of hypercapnia. Basal cerebral blood flow did not change significantly in response to local tetrodetoxin, and also after local and systemic administration of indomethacin. Hypercapnia increased cerebral blood flow by 25.9±3.9% before and by 24.3±6.5% after administration of TTX and by 22.1±7.1% before and by 18.2±6.3% after administration of indomethacin. In the rabbit, prostaglandin and regional nerves had no role in regulation of basal cerebral blood flow, nor did they contribute to cerebral vascular dilatation during hypercapnia.