The active forms of tetanus and botulinum neurotoxins, released from the precursor molecule by specific proteolysis and reduction, block the release of neurotransmitters via a Zn(2+)-dependent protease activity. VAMP/synaptobrevin, an integral membrane protein of the synaptic vesicles, is cleaved at a single site by tetanus and botulinum B, D and F neurotoxins. The unique sequence, mechanism of activation and site of activity of clostridial neurotoxins mark them out as an independent group of Zn(2+)-endopeptidases.