Responses to vasodilator agents were compared in helical strips of mesenteric beagles of different ages (30 days, 3 months, 2 years and 12 years old), precontracted with prostaglandin F2 alpha (PGF2 alpha). Relaxations induced by isoprenaline and adenosine were related inversely to age, whereas those induced by PGI2 and K+ (5 mM) did not alter with age. Acetylcholine-induced relaxations were less in the arteries from the aged (12 year old) beagles than in those from the younger beagles. Histamine-induced relaxations related directly to age between 30 days and 2 years. Acetylcholine-induced relaxation was reversed to a contraction in infant (30 day old) beagle arteries by removal of the endothelium, and significantly attenuated in the older beagle arteries. In adult (2 year old) and aged beagle arteries, removal of the endothelium attenuated the histamine-induced relaxation. Treatment with indomethacin reversed the histamine-induced relaxation to a marked contraction in aged beagle arteries. It may be concluded that responses mediated by beta-adrenoceptors and P1-purinoceptors are less in aged mesenteric arteries than in those from the younger beagles, whereas responses mediated by PGI2 receptors and the electrogenic Na+ pump do not alter with age. The release of endothelium-derived relaxing factor(s) by acetylcholine appears to be inversely related to age. However, the release of PGI2 possibly caused by histamine may be less in infant beagle mesenteric arteries than in those from the older beagles.