Arteriolar responses to the vasodilator adenosine and to the vasoconstrictor norepinephrine (NE) were examined in small bundles of extensor digitorum longus muscle grafted onto the cheek pouches of hamsters. Responses of arterioles to topically applied adenosine or NE were measured from 30 to 180 days after grafting and compared with the response of arterioles in control cheek pouches. Verapamil and potassium chloride (KCl) were applied to 120- and 180-day grafts to determine the response of arterioles to vasoactive agents not mediated by receptors. Arterioles in grafted muscle did not respond to adenosine until 60 days. The response increased with time but was significantly less than the control value even after 180 days. Arterioles in grafts did not respond to NE until 90 days. At both 90 and 120 days the degree of constriction in response to NE was not uniform along the length of a given arteriole (punctate response). By 180 days, the response of a given arteriole to NE was uniform but significantly less than the control value. In 120- and 180-day grafts the responses of arterioles to verapamil and KCl were similar to the responses of arterioles to adenosine and NE, respectively. We conclude that the diminished response of arterioles in small EDL muscle grafts to vasoactive agents may be caused by either a structural or a functional impairment in the smooth muscle layer of arterioles.