Vascular smooth muscle function does not necessarily deteriorate with advancing age. However, although base-line function may be well maintained, the ability to adapt to stress may decline. Therefore we tested the hypothesis that development of denervation supersensitivity may be impaired in older animals. Fischer-344 rats (6, 12, 20, 24 and 27 months old) were treated with reserpine 0.3 or 0.4 mg/kg i.p. for 7 days, a dose which was sufficient to deplete fully vascular norepinephrine content. Isometric contractile responses to phenylephrine and serotonin of isolated tail artery rings were determined. In the oldest animals studied, 27 months, chronic reserpine treatment resulted in depressed tail artery contractile responses, perhaps due to a toxic effect of the reserpine treatment. Reserpine-induced supersensitivity, reflected by a decreased EC50, developed to both agonists at all other ages studied. For serotonin, the degree of reserpine-induced supersensitivity did not change with age. However, for phenylephrine, the shift in the concentration-response curve after reserpine treatment was less in 6-month-old rats as compared to all other ages. There was no change in the development of supersensitivity from 12 to 24 months of age. These findings suggest that the development of reserpine-induced supersensitivity is not impaired in blood vessels of older animals and that the ability to adapt to changing conditions is also maintained with age.