Summary Evidence that nitrendipine (2,6-dimethyl-3-carbomethoxy-5 -carbomethoxy-4-(3-nitropheny 1) 1,4-dihydropyridine) and other 1,4-dihydropyridines interact at a specific site to antagonize Ca2+ channel function is reviewed. This evidence derives from electrophysiologic and pharmacologic studies and is confirmed by [3H]radioligand binding to excitable tissues. The availability of 1,4-dihydropyridine activator ligands including BAY K 8644 (2,6-dimethyl-3-carbomethyl-5-nitro-4-(2-trifluoromethyl) 1,4-dihydropyridine) suggests that this site is intimately concerned with Ca2+ channel regulation. The actions of the 1,4-dihydropyridine ligands are discussed with particular reference to their tissue selectivity and the functional relationships of binding sites to Ca2+ channels.