[3H]-Nimodipine a potent calcium channel blocker, binds to an apparently homogenous population of receptors in guinea-pig brain membranes (KD=0.62 nM, Hill coefficient or approximately 1.0). Diltiazem (10(-5) M) lowers the KD for [3H]-nimodipine by a factor of 3 without changing the maximum number of binding sites. Diltiazem decreased the dissociation rate constant of the nimodipine-receptor complex from 0.18 min-1 to 0.049 min-1 and altered the pharmacological profile as revealed by displacement studies with (-) and (+) verapamil, (-) and (+) prenylamine and 1,4 dihydropyridines. In conclusion [3H]-nimodipine binding can be utilized as a tool to evaluate complex molecular interactions between calcium channel blockers.