alpha-Latrotoxin is a potent stimulator of neurotransmitter release from nerve terminals. High affinity membrane alpha-latrotoxin receptor was purified in an active binding form. It is a membrane glycoprotein (M(r) 160,000-220,000) which may be complexed to a smaller polypeptide (M(r) 29,000). The structure of the receptor protein suggests that it may be a synapse-specific cell recognition molecule. Intracellularly, the alpha-latrotoxin receptor interacts with synaptotagmin, a calcium- and phospholipid-binding protein specifically localized in the synaptic vesicle membrane. This interaction may be important for targeting of synaptic vesicles to presynaptic release sites.