Tobacco smokers have an increased risk of cardiovascular disease; this is likely associated to an enhanced catecholamine release by circulating nicotine. Here, we have explored how low concentrations of nicotine in the range of those found in the blood of tobacco smokers, might affect the release of catecholamines in bovine chromaffin cells. We have combined patch-clamp and Ca(2+) imaging techniques to study cell excitability, cytosolic Ca(2+) transients, vesicle movement, and secretory responses. We found that low concentrations of nicotine (1.5-3 microM) did not enhance catecholamine release by themselves. However, they drastically augmented the catecholamine release response triggered by a supramaximal K(+) depolarising pulse. Furthermore, low nicotine concentrations caused slight depolarisation with superimposed action potentials, a transient elevation of [Ca(2+)](c) and augmented Ca(2+)-dependent vesicle motion underneath the plasmalemma. We suggest that low nicotine concentrations overload the secretory machinery with secretory vesicles, which cause chromaffin cells to respond with an exaggerated adrenaline release into the circulation during stress. This might contribute to the higher cardiovascular risk of tobacco smokers.