To define the functional role of postsynaptic alpha-adrenoceptors in urethral smooth muscle, we examined the effects of various alpha-adrenergic agonists and antagonists on the contractile properties of the isolated urethra of male and female rabbits and quantified the population of alpha 1-and alpha 2-adrenoceptors, using radioligand receptor binding techniques. Norepinephrine (NE), epinephrine, and phenylephrine, an alpha 1-adrenergic agonist, induced increases in contractile force in both the male and female urethra. Clonidine, an alpha 2-adrenergic agonist, caused a relatively large contractile response in the female urethra but only a small contractile response in the male urethra. Receptor binding studies indicated that the male urethra contains almost equal amounts of alpha 1- and alpha 2-adrenoceptors (32 vs. 34 fmol/mg, respectively), whereas the female urethra contains a significantly greater density of alpha 2- than alpha 1-adrenoceptors (122 vs. 34 fmol/mg, respectively). Our studies indicate that both alpha 1- and alpha 2-adrenoceptors cause contractile responses in male and female rabbit urethra; and the greater response to alpha 2-agonist in female than male urethra is correlated with a higher density of alpha 2-adrenoceptors in this tissue.