Abstract-The tetanus toxin light ehain blocks ealcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zine binding motif of the tetanus toxin light chain is essential for the inhibition of ellocytosis, in the rat. The zine chelating agent dipicolinic acid as weil as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesic1e membrane protein synaptobrevin land 2, prevent the effect of the tetanus toxin light ehain.Our results indicate that zine bound to the zine binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that c1eavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules.