The present study was designed to test the hypothesis that prostaglandins(PGs) contribute to the increased arterial baroreflex sensitivity in neonates when compared to adults. To test this hypothesis, (a) we measured PGE2 and PGI2 levels in carotid sinus of newborn (NB) (n=6) and adult (A) sheep (n=5) and (b) using an isolated carotid sinus preparation, we determined the changes in carotid sinus nerve activity (CSNA) in NB (n=6) and A (n=3) sheep in response to PGI2 and following inhibition of PG synthesis with indomethacin. First, carotid sinus PGE2 and PGI2 levels were significantly (p<0.05) higher in NB (145±36 and 63±10 pg/ml, respectively) than in A (23±4 and 3±1 pg/ml, respectively). Second, PGI2 (20 to 80 μM) did not modify the CSNA response to progressive rises in carotid sinus pressure (CSP) in NB. A small but significant increase (p<0.05) in maximal CSNA (+5.8±2.2%) was observed in A. Third, indomethacin (10 to 80 μM) decreased the sensitivity(gain) of the CSNA response to rise in CSP (from 0.95±0.14 to 0.56±0.10%/mmHg at 80 μM) and reduced maximal CSNA by 48±9% in NB (p<0.05), but did not alter CSNA in A. These results demonstrate that endogenous PG levels are high in NB carotid sinus and are important modulators of arterial baroreceptor activity in NB, but not in A. Sensitization of baroreceptors by PGs may explain the increased baroreflex sensitivity in NB compared with A sheep.