1 The effects of six calcium entry blockers belonging to the dihydropyridine (isradipine or PN 200-110, nifedipine, nicardipine), verapamil (D888 or desmethoxyverapamil, D600 or gallopamil) and diltiazem classes were investigated on isometric spontaneous contractions and contractions induced by high-K+ solutions, noradrenaline, acetylcholine and caffeine. 2 The rank order of potency was PN 200-110>nicardipine=nifedipine=D888>D600>diltiaz-em from experiments on spontaneous contractions and high-K+ induced contractions. With depolarized preparations, the concentration-response curves for nicardipine, PN 200-1 10, nifedipine and D600 were significantly shifted to the left indicating that the calcium entry blockers show voltagedependent inhibitory properties. This effect was not significant with D888 and diltiazem. 3 All the calcium entry blockers strongly reduced the noradrenaline (NA)-and acetylcholine (ACh)-induced contractions at concentrations which produced complete inhibition of spontaneous contractions. They had a slight effect on caffeine-induced contractions. 4 In Ca2+-free, EGTA-containing solutions, both ACh, NA and caffeine produced transient contractions, the amplitude of which could be taken as a measurement of the amount of internal calcium present in a drug-sensitive calcium store. The filling ofthe calcium store was maximal after 10-12 min ofcalcium loading in 2.1 mM Ca2", while the depletion was complete after 4-6 min ofperfusion in Ca2"-free solution.5 At concentrations which abolished spontaneous contractions, PN 200-110, nifedipine, D888 and D600 had no appreciable effect on contractions evoked in Ca2"-free solutions by ACh, NA and caffeine. When added in Ca2+-containing solutions diltiazem and, to a lesser extent, nicardipine strongly reduced the contractions evoked in Ca2 -free solutions, suggesting that they inhibited the filling of the internal calcium store. 6 These results indicate that the six calcium entry blockers are potent inhibitors of calcium influx through voltage-dependent calcium channels. Two of them (diltiazem and nicardipine) may exert an additional effect to depress contractions dependent on intracellular calcium release.