The NSF, SNAP, and SNAP receptors are key elements of the intracellular membrane fusion machinery. We use an affinity purification scheme, based on the function of SNAP receptor in assembling 20S fusion particles from NSF and SNAP proteins, to purify SNAP receptors from brain. Remarkably, each of the four SNAP receptors (or, SNAREs) thus delineated resides in synapses, with one receptor originating in the synaptic vesicle and another in the presynaptic plasma membrane that is targeted for fusion. This suggests a simple mechanism in which the general NSF/SNAP fusion machinery can assemble to bridge partner membranes in a complex containing elements of both vesicle and target membranes, and implies that similar fusion machines drive both constitutive fusion (ER-->Golgi-->surface and endocytosis) and regulated exocytosis. The vesicle (v-SNARE) and the target-associated t-SNAREs from the synapse are each members of compartmentally-specific families of membrane proteins found in yeast, animal cells, and neurons, thus raising the possibility that v-SNAREs and t-SNAREs encode specificity in membrane fusion processes that utilize a common mechanism.