The epsilon-opiate receptor of the electrically stimulated rat vas deferens has been characterized by means of beta-endorphin, its fragments and derivatives thereof, as well as by its tolerance development. The data provide evidence for the uniqueness of the epsilon-receptor as compared to mu- and delta-receptors of the guinea-pig ileum and the mouse vas deferens, respectively. It appears that an activation of the epsilon-receptor requires at least the beta-endorphin sequence 1-21, which sharply contrasts with the relatively high sensitivity of mu- and delta-receptors to much shorter fragments of this opioid peptide. Furthermore, after chronic exposure of rats to etorphine, the isolated vas deferens shows a dramatic loss of sensitivity to mu-receptor agonists, but only a moderate decrease in sensitivity to beta-endorphin. The presented data contribute to the characterization of a distinct novel type of opiate receptor, the epsilon-receptor.