Adrenomedullary cells and autonomic ganglion cells originate from the neural crest. Both cell types synthesize, store and release catecholamines; however, their structural and functional properties are distinctly different. Aloe and Levi-Montalcini have shown in vivo that when the adrenal medulla is exposed to exogenous nerve growth factor (NGF) most cells differentiate into neuronal cells substantially similar to sympathetic neurones. Experiments in vitro have also shown that neonatal as well as adult adrenal chromaffin cells and their neoplastic correlate (PC12 cells) undergo neurone-like morphologic differentiation in response to NGF. From these morphological and biochemical studies alone, however, it remains uncertain whether the functional neuronal transformation is also accompanied. We report here that the adrenal chromaffin cells in culture can differentiate into neuronal cells having functional synapses which were found to be cholinergic in nature. Furthermore, the type of synaptic vesicles in the newly formed synapses was apparently dependent upon K+ levels in the culture medium.