Antibodies that recognize dihydropyridine (DHP) calcium entry blockers were elicited from rabbits. A sensitive and specific radioimmunoassay for dihydropyridines was developed and its specificity compared to the DHP binding site in skeletal muscle membranes. The antibody bound [3H]nitrendipine with a higher affinity (KD= 0.155 nM) than did the DHP receptor of skeletal muscle (KD = 1-3 3 nM); however, in contrast to the DHP receptor, the antibody recognized only those DHP drugs with meta-nitrophenyl substituents at the 4-position on the DHP ring. Both the antibody and receptor exhibited stereospecificity, with each site recognizing the (+)-isomer of nicardipine as the more potent. This antibody should prove useful in our studies of some potentially irreversible DHP molecules.