The temporal resolution of carbon-fiber microelectrodes has been exploited to examine the plasticity of quantal secretory events at individual adrenal medullary cells. The size of individual quantal events, monitored by amperometric oxidation of released catecholamines, was found to be dependent on the extracellular ionic composition, the secretagogue, and the order of depolarization delivery. Release was observed with either exposure to 60 mM K+ in the presence of Ca2+ or exposure to 3 mM Ba2+ in solutions of different pH, with and without external Ca2+. Ba2+ was demonstrated to induce Ca(2+)-independent exocytotic release for an extended period of time (> 4 min) relative to release induced by K+ (approximately 30 s), which is Ca2+ dependent. In all cases, simultaneous changes of intracellular divalent cations, monitored by fura-2 fluorescence, accompanied quantal release and had a similar time course. Exocytosis caused by Ba2+ in Ca(2+)-free medium had a larger mean spike area at pH 8.2 than at pH 7.4. When Ba(2+)-induced spikes measured at pH 7.4 were compared, the spikes in Ca(2+)-free medium were found to be broader and shorter but had the same area. Release induced by K+ after exposure to Ba2+ was comprised of larger quantal events when compared with preceding K+ stimulations. Finally, spikes obtained with Ba2+ exposure at an extracellular pH of 5.5 had a different shape than those obtained in more basic solutions. These changes in spike size and shape are consistent with the interactions between catecholamines and other intravesicular components.