We have investigated here whether 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 the responses elicited by 100ACh or 100K⁺by 2- to 3.5-fold. This effect was suppressed by mecamylamine and by Ca²⁺deprivation, was developed with a half-time ( t_1/2) of 1 min, and was reversible. The nicotine effect was mimicked by threshold concentrations of ACh, choline, epibatidine, and oxotremorine-M but not by methacholine. Threshold concentrations of K⁺caused lesser potentiation of secretion compared with that of 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.