Pre- and postsynaptic α-adrenoceptors in autoperfused rabbit hindlimbs were examined employing the yohimbine diastereomers rauwolscine and corynanthine, as well as other drugs with varying selectivities for α1- and α2-adrenoceptors. Vasoconstrictor responses were elicited by sympathetic nerve stimulation and by intraarterial injection of agonists. The α2-selective antagonist rauwolscine (10-7 and 10-6 M) reduced responses to injected noradrenaline (mixed α1- and α2-agonist) but not to injected phenylephrine (α1-selective agonist); rauwolscine (10-6 M) actually enhanced nerve-mediated responses. Corynanthine (α1-selective antagonist) was about equipotent against agonist- and nerve-mediated responses. In another series of experiments, rauwolscine (10-6 M) strongly antagonized the response to xylazine (α2-selective agonist), antagonized the responses to α-methylnoradrenaline and noradrenaline (mixed agonists) less strongly, and did not affect the response to phenylephrine. Conversely, prazosin (α1-selective antagonist, 10-8 M) strongly antagonized phenylephrine, antagonized noradrenaline and α-methylnoradrenaline less strongly, and did not antagonize xylazine. Potentiation of neuroeffector responses by rauwolscine demonstrates the operation of an endogenous α2-toinhibition of noradrenaline release mediated by presynaptic α2-adrenoceptors. However, in comparison with previous in vitro results on rabbit pulmonary artery, the potentiation was small due to the presence of postsynaptic α2-adrenoceptors.