Several Ca channel blockers--verapamil, nifedipine, nimodipine (Bay e 9736), and nitrendipine (Bay e 5009)--had different effects on Ca transport by sarcoplasmic reticulum vesicles from either skeletal or cardiac muscle. Both nimodipine and nitrendipine (1 X 10(-4) M) stimulated Ca sequestration in the absence of a Ca-precipitating anion by either cardiac or skeletal sarcoplasmic reticulum (SR), with nitrendipine being the more potent stimulator. Nifedipine (1 X 10(-4)M) had no significant effect, whereas at higher concentrations (3 X 10(-3) M) verapamil inhibited the Ca sequestration reaction. Nitrendipine stimulated Ca ATPase and Ca sequestration to a similar extent. Stimulation of Ca sequestration by nitrendipine was dependent on drug/membrane phospholipid mole ratios of between 1:4 and 3:1, as well as absolute drug concentration thus suggesting an interaction of the drug with membrane phospholipids. Nifedipine, nitrendipine, nimodipine, and verapamil (1 X 10(-4)M) had no effect on phosphate-supported Ca uptake by skeletal SR, whereas higher concentrations of verapamil (3 X 10(-3)M) inhibited this reaction by either cardiac or skeletal SR. The results of this study suggest that (a) Ca channel blockers have complex and variable effects on SR membranes, (b) these effects are similar in cardiac and skeletal SR, and (c) the effects are in part mediated through an interaction with membrane phospholipids or hydrophobic portions of the Ca ATPase.