To characterize the role of prostaglandins (PG) in the regulation of basal cerebral blood flow (CBF) in the newborn, we determined the effects of four nonsteroidal antiinflammatory drugs, indomethacin (3 mg/kg, n = 8 and 10 mg/kg, n = 5), aspirin (65 mg/kg, n = 6), ibuprofen (30 mg/kg, n = 8), and naproxen (15 mg/kg, n = 6), on CBF, cerebral metabolism, and cerebrovascular PG in conscious 1- to 3-d-old piglets. Drugs and vehicle (n = 8) were injected i.v., and measurements were made 5 min before and 20 and 60 min after injections. Neither the vehicle nor any of the nonsteroidal antiinflammatory drugs exerted significant effects on mean arterial blood pressure and on blood gases and pH. All four drugs, with the exception of indomethacin at the lower dose (3 mg/kg), decreased PG to nearly undetectable levels within 20 min; the low dose of indomethacin caused a small decrease (18-32%) in PG at 60 min. However, the effects of these agents on CBF were diverse. CBF increased after the administration of aspirin, decreased to almost the same extent after both low and high doses of indomethacin, and did not change after the administration of ibuprofen and naproxen. Cerebral metabolic rate for oxygen was increased by aspirin but was unaltered by the other drugs. The data suggest that PG may not play a critical role in the regulation of basal CBF in the newborn animal and that certain nonsteroidal antiinflammatory drugs may have additional actions unrelated to the inhibition of PG synthesis.