The present study examined the utility of the rat vas deferens preparation as a bioassay for σ site ligands. σ Ligands such as (±)-pentazocine, phencyclidine (PCP) and (+)-SK&F 10047 potentiated neurogenic twitch contractions. However, neither the order of potency nor the absolute potency of (±)-pentazocine and (+)-SK&F 10047 correlated with their affinity at central σ sites. Furthermore, another potent σ ligand, ditolyl-ortho guanidine (DTG) neither affected neurogenic twitch contractions nor inhibited twitch potentiation by PCP or (+)-SK&F 10047 at concentrations up to 30 μmol/1. These data indicate that the rat vas deferens is not a useful bioassay for the evaluation of σ ligands. PCP, (+)-SK&F 10047 and (±)-pentazocine probably enhance neurogenic contractions in rat vas deferens primarily by inhibition of the neuronal uptake of noradrenaline.