The effects of a number of calcium channel effectors on Ca2+ uptake by rat liver plasma membrane vesicles was examined. Nifedipine, verapamil and diltiazem had to be present at 1 mM in order to produce > 50% inhibition of Ca2+ uptake. The two structurally similar 1,4-dihydropyridines, nicardipine and nisoldipine exhibited opposite effects; nicardipine inhibited while nisoldipine stimulated Ca2+ uptake. The results show that low concentrations (microM) of calcium channel blockers of excitable cells have little effect on Ca2+ uptake by liver plasma membrane vesicles consistent with earlier findings of others that voltage-gated calcium channels are absent in hepatocytes. However, the opposite effects of higher concentrations (ca. 1 mM) of nicardipine and nisoldipine on Ca2+ uptake suggest a discriminatory action that might be useful in studying further the mechanism of passive Ca2+ uptake by these membrane vesicles.