Interactions between synaptic vesicles and the presynaptic membrane which accompany transmitter release were examined at excitatory, cholinergic synapses in bullfrog sympathetic ganglia. Ganglia were fixed at rest or during electrical stimulation of the preganglionic axons and then were either thin-sectioned or freeze-fractured. Release of transmitter for brief periods is accompanied by selective depletion of four-fifths of the synaptic vesicles aligned at active zones, an overall loss of half of the synaptic vesicles in the terminals, and synaptic vesicle openings at active zones. These findings are consistent with the hypotheses that synaptic vesicles which are ready to be released are aligned at active zones and that these vesicles fuse with and add their membrane to the presynaptic membrane as they release transmitter. Larger vesicles with dense cores also contact and open onto the presynaptic membrane at the active zone, appearing to release their contents by exocytosis. The arrangement of intramembrane particles at fractured postsynaptic specializations resembles that at other excitatory, cholinergic synapses.