1,4-Dihydropyridines are a new class of compounds believed to bind specifically and with high affinity to voltage-dependent calcium channels1–5. They may be the first example of a ligand of use in the extraction1,2and purification3of the Ca channel. Although Ca channels and dihydropyridine receptors are found in many tissues, the richest and most convenient source is skeletal muscle4. Functionally, 1,4-dihydropyridines such as nifedipine and nitrendipine block Ca channels6–11; this effect is believed to form the basis for their clinical importance as Ca antagonists in relaxing vascular smooth muscle6. But where currents through Ca channels can be measured directly7–10, the block has required 100–1,000 times higher concentrations of dihydropyridine than necessary for the saturation of dihydropyridine binding sites1,5. This discrepancy has remained unresolved because the study of pharmacological effects on Ca channels has required intact cells, while it has been difficult to investigate binding in other than cell-free preparations. Here we describe a method for measuring dihydropyridine binding to intact skeletal muscle and we compare our results with voltage-clamp measurements of Ca-channel block. We conclude that less than a few per cent of the binding sites in skeletal muscle represent functional Ca channels, contrary to general belief.