Treatment with 100 or 250 μM ZnCl₂ irreversibly blocked neurotransmission in the Torpedo electric organ by inhibiting acetylcholine (ACh) release. In Zn²⁺-treated tissue, release failure did not result from impairment of Ca²⁺ entry since stimulation still provoked an accumulation of Ca²⁺. Also pretreatment of isolated synaptosomes with Zn²⁺ inhibited to the same extent the release elicited by KCl-evoked depolarisation and the release elicited by using the Ca²⁺ ionophore A23187. On the other hand, after application of A23187, Zn²⁺ by itself efficiently triggered ACh release from synaptosomes. This dual effect of Zn²⁺ was also observed to occur in proteoliposomes equipped with mediatophore (a protein of the presynaptic membrane characterised by its capability to support Ca²⁺-dependent transmitter release). Hence, Zn²⁺ mimicked two fundamental actions of Ca²⁺ on nerve terminals, which are: (1) the immediate activation of release, and (2) a more slowly developing desensitisation of release. Zn²⁺ was more powerful than Ca²⁺ for both actions. It is concluded that the dual action of Zn²⁺ on the mediatophore protein accounts at least in part for its complex effects on neurotransmission.