We used a combination of advanced optical imaging and cryogenic electron microscopy to explore membrane fusion between synthetic membranes that contained reconstituted synaptic proteins, including synaptotagmin and a family of protein receptors called SNAREs. When calcium ions were injected into the synthetic system, the basic characteristics of neurotransmitter release ' such as membrane fusion on a millisecond time scale ' was observed. Contrary to some theories of membrane fusion, the fastest fusion events did not begin or proceed via a discernible hemifusion intermediate state. Rather, these events proceeded from a 'point contact' state in which the membranes were close to each other (just 1-5 nm apart) without being fused, and were ready to undergo fast fusion once the calcium ions had been injected. When we introduced a protein called complexin, which is known to be important for fast neurotransmitter release in vivo, we observed more immediate fusion events and fewer events that involved a hemifusion intermediate.