The prostaglandin H-synthase inhibitor in-domethacin decreases cerebral blood flow (CBF) in newborn pigs. The duration of this effect on CBF has not been established in piglets in the awake state. The purpose of the study was to determine in awake piglets the duration of cerebral vascular responses to a single dose of indo-methacin and the CBF responses to a second dose of indomethacin. Two groups of animals were studied. Newborn pigs 3–5 d old were instrumented the day before experiments. On the next day, sagittal sinus catheters were placed after the piglets were given local anesthesia. The experiments were performed on unanesthetized piglets that were put in a cloth sling and fed via an orogastric tube. In the first group of piglets (n = 8), the baseline CBF (microspheres) and cerebral metabolic rate for oxygen (CMRO2) measurements were made 30 min after sagittal sinus catheter placement. Indomethacin (5 mg/kg i.v.) was then given slowly over a 5-min period, and CBF and CMRO2measurements were made at 10, 60, 120, and 240 min. Total CBF (mean ± SEM) decreased significantly after indomethacin administration from 98 ± 12 mLmin−1100 g−1to 50 ± 3, 56 ± 7, and 70 ± 11 mLmin−1100 g−1at 10, 60, and 120 min, respectively. The total CBF returned to baseline levels at 240 min (101 ± 16 mL−1min−1100 g−1). After indomethacin administration, the CMRO2decreased significantly from the baseline level of 3.57 ± 0.52 mL O2/100 g−1min−1to 2.50 ± 0.39, 2.69 ± 0.52, and 2.41 ± 0.31 mL O2/100 g−1min−1at 10, 60, and 120 min, respectively. The CMRO2returned to baseline by 240 min (3.09 ±0.46 mL O2/100 g−1min−1). In the first group of piglets, we observed maximum CBF responses between 10–60 min of indomethacin administration and return of CBF to baseline values within 4 h. Therefore, in another group of piglets (n = 10) we determined the effect of a repeated dose of indomethacin on CBF. The first baseline CBF measurements were made, and then indomethacin (5 mg/kg i.v.) was given. The CBF measurements were repeated at 30 min. Four hours later, a second baseline CBF determination was made, and a second dose of indomethacin (5 mg/kg i.v.) was administered. Thirty minutes after the second dose of indomethacin, CBF was measured again. Total CBF decreased significantly (p < 0.05) 30 min after the first dose of indomethacin (91 ± 10 to 52 ± 5 mLmin−1100 g−1). By 4 h, total and regional CBF returned to baseline values (NS). With the second dose of indomethacin, total CBF again decreased significantly (p < 0.05) from baseline values (from 77 ± 4 to 55 ± 6 mLmin−1100 g−1). We conclude that i.v. administration of indomethacin at 5 mg/kg to unanesthetized piglets results in decreased CBF and CMRO2, which return to baseline levels by 4 h after treatment, and that a second dose of indomethacin also results in a decrease in CBF similar to that evoked by the first dose.