The Ca2+channel antagonists D-600, diltiazem, and nifedipine are competitive antagonists of Ca2+responses in K+-depolarized guinea pig taenia coli and rat mesenteric artery preparations. pA2values for D-600, diltiazem, and nifedipine in taenia coli were 8.28, 7.44, and 9.27, respectively and in mesenteric artery, 9.6, 7.83, and 10.4, respectively. The combination of nifedipine plus diltiazem gave in both tissues antagonism greater than that calculated on the basis of additivity. This suggests, consistent with published3H-Sabelled radioligand binding data, that diltiazem and nifedipine interact at distinct sites. However, the combination nifedipine plus D-600 yielded antagonism consistent with additivity of response.