Mechanisms underlying age-dependent changes in vasodilator responses to beta-adrenergic drugs are poorly understood. The aim of the current study was to compare responses to isoproterenol (a non-selective beta-adrenergic receptor agonist) in phenylephrine or KCl precontracted aortic rings from 3 week and 3 month old male Wistar rats. Both the mechanism and the subtype of beta-adrenergic receptor underlying the response to isoproterenol in the both age groups were examined. Endothelial removal, pre-contraction with KCl (40 mM), pre-treatment with tetraethylammonium or with N(omega)-Nitro-L-arginine methyl ester inhibited the vasodilator response to isoproterenol only in aortic rings from older rats. The inhibition was total when TEA and L-NAME were administered together. In both age groups the response to isoproterenol was unaffected by the beta1-adrenergic antagonist CGP20712A, but was significantly inhibited by ICI 118551 (a beta2-adrenergic-antagonist) and to a greater extent by SR 59230A (a non-selective beta 3-adrenergic antagonist), the inhibition being more evident in the older rats. Unlike younger rats, in older animals the response to isoproterenol was partially dependent on endothelial nitric oxide and on K+ channels. In both age groups, beta2- and beta3-, but not beta1-adrenergic receptors were involved. The degree of relative participation of beta2 and beta3 adrenergic receptors may change with age and explain the differences in response to isoproterenol.