We have investigated here if a preconditioned stimulation of nicotinic and muscarinic receptors augmented the catecholamine release responses elicited by supramaximal 3-s pulses of 100 µM acetylcholine (100ACh) or 100 mM K⁺ (100K⁺), applied to fast-perifused bovine adrenal chromaffin cells. Threshold concentrations of nicotine (1-3 µM) that caused only a tiny secretion, did however augment by 2-3.5-fold the responses elicited by 100ACh or 100K⁺. This effect was suppressed by mecamylamine and by Ca²⁺ deprivation, developed with a 1/2 of 1 min and was reversible. The nicotine effect was mimicked by threshold concentrations of acetylcholine (ACh), choline, epibatidine and oxotremorine-M but not by methacholine. Threshold concentrations of K⁺ caused lesser potentiation of secretion, as compared with threshold nicotine. The data are compatible with an hypothesis implying: (1) that continuous low-frequency sympathetic discharge places chromaffin cells at the adrenal gland in a permanent "hypersensitive" state; and (2) this allows an explosive secretion of catecholamines by high-frequency sympathetic discharge during stress.