The prejunctional activities of S-3341 and clonidine have been studied in the transmural field-stimulated epididymal part of the rat vas deferens. Both S-3341 and clonidine inhibited these neuronally induced contractions. At high concentrations, these agonists induced spontaneous contractions in the preparation, which were abolished by 10(-7) M prazosin. The inhibitory effects of S-3341 and clonidine were antagonized in a competitive manner by rauwolscine and were found not to be modified in a statistically significant manner by 10(-7) M prazosin. The pA2 values of rauwolscine against S-3341 and clonidine were the same, indicating the receptors influenced by these drugs were the same also. However, the efficacy of S-3341 is lower than that of clonidine (by a factor of approximately 100). This lower efficacy of S-3341 at the prejunctional level could be linked to the lack of a sedative effect of this compound at therapeutic concentrations.