In the substantia nigra, acetylcholinesterase (AChE) has non-cholinergic action on dopaminergic neurons. The subset of neurons particularly sensitive to AChE are characterized by functionally active apical dendrites extending into the pars reticulata and generating a powerful calcium conductance. This study thus attempted to establish directly the importance of these dendrites regarding the action of AChE. Segregation of the pars compacta from the pars reticulata did not affect the AChE-induced hyperpolarization on this sub-set of dopaminergic neurons. However, the ionic basis of the hyperpolarization was related to the integrity of the neurons: AChE caused an opening of potassium channels in intact cells. On the other hand when the pars reticulata containing apical dendrites was removed, an action of AChE involving the closure of calcium/sodium channels was revealed. The results demonstrate that the net effect of AChE need not be related to any particular segment of the dopaminergic neurons, whereas the nature of the mechanism underlying that effect depends on the presence, or otherwise, of the apical dendrites.