In isolated and enriched guinea pig parietal cells the inhibitory effects of the calcium channel antagonists verapamil and gallopamil on 14C-aminopyrine uptake (= H+ secretion) have been analyzed. Both verapamil and gallopamil inhibit acid secretion in a concentration-dependent manner with an IC50 of 12.1 and 10.9 mumol/l respectively. The type of inhibition is noncompetitive in nature. Verapamil inhibits the acid response to histamine, dibutyryl-cAMP, and KCl with IC50 values not significantly different from each other. Exposure of the cells to verapamil and subsequent washing enhances the acid response to histamine for an unknown reason. It is concluded that the calcium channel antagonists verapamil and gallopamil inhibit acid secretion in vitro by interfering with the parietal cell proton pump, the K+/H+-ATPase.