Effects of tripelennamine, N, N-dimethyl-N', N'-dibenzylethylenediamine (DBED) and N, N-dibenzyl-N', N'-dimethyl-1, 2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of intact and reserpinized guinea pigs to acetylcholine were examined. Increase in sensitivity to acetylcholine induced by tripelennamine, DBED and DBPD was attenuated remarkably by reserpine. Tripelennamine- and DBED-induced increases in Ca²⁺-contractions were not affected by reserpine. Acetylcholine-contractions in Ca²⁺-free Tyrode solution were inhibited by reserpine, but K⁺-contractions in Ca²⁺-free Tyrode solution were not affected by reserpine. Tripelennamine- and DBED-induced increases in acetylcholine- and K⁺-contractions in Ca²⁺-free Tyrode solution were attenuated or abolished by reserpine. DBPD decreased cholinesterase activity of vas deferens of guinea pig, but DBED did not. These results suggest that, although the Ca²⁺-storage site utilized for acetylcholine-contraction is different from that for K⁺-contraction, tripelennamine- and DBED-induced increase in Ca²⁺-release from superficial Ca²⁺-binding sites induced by acetylcholine and K⁺ is inhibited by reserpine. It is also estimated that DBPD-induced supersensitivity to acetylcholine might be due to the inhibition of cholinesterase activity. However, the mechanism of inhibition of DBPD-induced supersensitivity by reserpine remained obscure.