Synaptophysin is an integral membrane protein of synaptic vesicles found in neurons and endocrine cells. Synaptophysin monomers associate into hexamers forming a large conductance channel. We present an analysis of synaptophysin from the nervous system of the marine ray Torpedo californica. Analysis of cDNA clones reveals a 62% amino acid similarity between the Torpedo and rat sequences. The 4 hydrophobic membrane spanning domains and the glycosylation site are conserved. In contrast, the two intravesicular loops connecting the membrane spanning regions, show varying degrees of sequence conservation, suggesting that portions of these domains may play critical functional roles. The carboxyterminal tail has been proposed to bind calcium and is a major site for tyrosine phosphorylation. The precise sequence of this region has almost completely diverged while the proline-tyrosine rich nature is maintained. Blotting studies reveal the RNA and the protein in nervous system tissues and demonstrate that the molecule copurifies with cholinergic synaptic vesicles.