The effects and interactions of pipecuronium and atracurium with diltiazem and verapalmil on the electrically-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat phrenic-hemidiaphragm preparation. Pipecuronium (3X10(-7) -4X10(-6)) and atracurium (10(-6) -3X10(-5) M) decreased the electrically-evoked twitch response, train-of-four and tetanus ratio in a dose-related fashion and the pipecuronium was more potent than atracurium. The inhibitory effects of pipecuronium and atracurium were potentiated by pretreatment of 5 uM diltiazem and verapamil, Ca++-channel blokers, in which the concentration of diltiazem or verapamil has no obvious effect on the twitch response itself. Futhermore, it is noteworthy that the inhibitory effects of pipecuronium and atraeurium were markedly potentiated by 150 uM hemicholinium pretreatment. On the basis of these findings, the results of present study suggests that the muscle relaxation by pipecuronium and atracurium is mediated by pre- and post-junctional receptor blockade, and that diltiazem or verapamil intensifies neuromuscular blockade produced by these musele relaxants. The potentiating effect of diltiazem or verapamil may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.