1. The effects of several ligands which interact with the sigma-binding site were studied on the electrically-evoked (0.1 Hz) neurogenic twitch contractions of the mouse isolated vas deferens. 2. (+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine [+)-3-PPP) (10(-8) - 10(-5) M), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10(-6)M), idazoxan (10(-6)M), cocaine (10(-6)M) or tyramine (10(-4)-3 x 10(-4)M), but was abolished by the dopamine D2-antagonist, sulpiride (10(-6)M). Therefore, in order to study the potentiating actions of sigma ligands, sulpiride (10(-6)M) was used to prevent any inhibitory actions mediated via dopamine D2-receptors. 3. In the presence of sulpiride (10(-6)M), haloperidol (10(-6)-10(-5)M), (+)-3-PPP (10(-6)-3 x 10(-4) M) and (+)-N-allyl-N-normetazocine [+)-SKF 10,047) (10(-5)-10(-4)M) each reversibly potentiated the neurogenic twitch contractions in a concentration-dependent manner. The rank order of potency was haloperidol greater than (+)-3-PPP greater than (+)-SKF 10,047. 4. The stereoisomers of 3-PPP displayed stereoselectivity with (+)-3-PPP being more potent than (-)-3-PPP. 5. At a concentration that did not potentiate the twitch contractions, (3 x 10(-7)M), haloperidol did not antagonize the potentiating action of (+)-3-PPP (3 x 10(-5)M). 6. 1,3-Di-O-tolyguanidine (DTG) (10(-8)-10(-5)M) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)-3-PPP (10(-5)-3 x 10(-5)M). 7. It is concluded that a-ligands potentiate neurogenic twitch contractions of the mouse isolated vas deferens via a site that is different from the central sigma-binding site.