Ion channels from bovine neurohypophysial secretory granules (NSG) were incorporated into artificial lipid bilayers. Specific antibodies against identified synaptic vesicle proteins were tested on such incorporated channel activity and on peptide release from rat permeabilized neurohypophysial terminals. Both the NSG cation channel and Ca(2+)-dependent release were inhibited by only SY-38, a monoclonal antibody directed against the C-terminus of synaptophysin. SY-38 and Ca(2+) altered both the gating and conductance of the NSG cation channel, but in opposite ways. The close correlation between SY-38 effects on Ca(2+)-dependent channel activity and release leads us to conclude that this synaptophysin-like NSG channel is directly involved in peptide secretion from these central nervous system terminals.