The existence of sigma receptors in the mouse, rat and guinea pig vasa deferentia has previously been proposed, although drug effects are inconsistent and generally occur only at high concentrations. The purpose of the present study was to evaluate lower, physiologically relevant concentrations of ligands for possible sigma effects on electrically stimulated twitch contractions in the mouse vas deferens (MVD). Putative sigma agonists and antagonists all inhibited 0.1 Hz electrically stimulated twitch contractions in nM concentrations. Inhibitory activity plateaued between 20 and 60% for all compounds except 1,3-di(2-tolyl)guanidine (DTG), which had a shallow concentration-effect curve. Subsequent to the plateau, higher concentrations (30 microM) of rimcazole and haloperidol fully inhibited electrically stimulated twitch contractions. There was no correlation between inhibitory potency or maximal effect in the MVD and binding potency at sigma sites in either MVD or guinea pig brain. The inhibitory effects of R(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ((+)3-PPP) or DTG on electrically stimulated twitch contractions were not antagonized by the putative sigma antagonists DTG, haloperidol, rimcazole or BMY-14802, nor by alpha 2-adrenoceptor, dopamine D1, dopamine D2 or opiate antagonists. Although the mechanism of sigma ligand effects in the MVD has not been established, the data caution against a presumption that effects of sigma ligands on electrically stimulated twitch contractions in this preparation are mediated by sigma receptors.