These studies were designed to investigate the relationship between cerebral prostanoid synthesis and pial arterial caliber in chloralose-anesthetized newborn pigs with normal blood gases and pH and during combined arterial hypoxia and hypercapnia. Piglets less than 5 days old were equipped with closed cranial windows to allow direct observation of pial vessels, application of prostaglandin E2, and sampling of cortical subarachnoid cerebrospinal fluid. We found that prostanoids accumulate in cerebrospinal fluid on the cortical surface. The only prostanoid detected in arterial blood was 6-keto-prostaglandin F1 alpha [442 +/- 74 pg/ml (radioimmunoassay)]. Only small quantities of 6-keto-prostaglandin F1 alpha (214 +/- 53 pg/ml) and thromboxane B2 (122 +/- 18 pg/ml) were found in cerebrospinal fluid from the cisterna magna. Higher concentrations of 6-keto-prostaglandin F1 alpha (1056 +/- 159 pg/ml), thromboxane B2 (229 +/- 64 pg/ml), and prostaglandin E2 (4235 +/- 269 pg/ml) were found in cortical subarachnoid fluid. In contrast to arterial and cisternal concentrations, the concentrations of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 in cortical subarachnoid fluid were increased reversibly by ventilation with 9% carbon dioxide, 10% oxygen, (6-keto-prostaglandin F1 alpha, 5436 +/- 1576 pg/ml; thromboxane B2, 694 +/- 122 pg/ml; and, prostaglandin E2, 12,455 +/- 3688 pg/ml). Further, pial arteries dilated in response to topical application of prostaglandin E2 at the concentration that was found in cortical subarachnoid fluid during combined hypoxia and hypercapnia. Systemic administration of indomethacin trihydrate (5 mg/kg) markedly reduced cortical subarachnoid fluid prostanoid concentrations and attenuated the pial artery vasodilation induced by combined hypoxia and hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)