SK&F 96365 (1-[3-(4-methoxyphenyl)propoxyl]-1 -(4-methoxyphenyl)ethyl-1H-imidazole HCl) (1-50 mu M), an inhibitor of receptor-mediated Ca2+ entry. reduced both acetylcholine (ACh)- and 56 mM K+ (high K+)-induced Ca-45(2+) influxes and catecholamine secretion in bovine adrenal chromaffin cells. However, SK&F 96365 at lower concentrations (1-3 mu M) inhibited only ACh-induced Ca-45(2+) influx and secretion but not their high K+-induction. In Na+-free medium, ACh-induced Ca-45(2+) influx and secretion were also considerably decreased by SK&F 96365 at low concentrations (1-3 mu M). These results suggest that in the chromaffin cells. not only voltage-sensitive calcium channels but also ACh receptor-operated calcium channels at least in part contribute to the influx of Ca2+ which triggers the catecholamine secretion from the cells when the cells are exposed by ACh.