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Publisher Summary Dopamine synapses in the striatum are much smaller than at the neuromuscular junction, and unless efficient mechanisms exist for its retention, diffusional efflux from the synapse is likely. To test this hypothesis in vivo , efflux evoked by a four-pulse, 100-Hz train applied to dopamine fibers in the medial forebrain bundle was compared with that evoked by a single pulse. The duration of a 100-Hz train is too rapid for appreciable uptake to occur. The observed release was 4 times the amplitude of a single pulse, providing strong evidence that dopamine normally exits the synapse during impulse flow. It has been concluded from experiments that dopamine normally escapes the synaptic cleft, diffuses into the extrasynaptic fluid, and then acts with remote receptors. Its extracellular diffusion is restricted to a few micrometers because of interaction with the dopamine transporter. The estimated amount of dopamine released per terminal per impulse from the single-pulse experiments was 1000 molecules, a value similar to that measured during release from a cultured neuron. The nonlinear relationship between dopamine release, stimulation current, and the external [Ca 2+ ] is exactly the relation anticipated for a quantized release probability associated with vesicles. Thus, according to the model used in the experiment, the quantized levels represent the population of terminals near the electrode shifting from 0 to 1 to 2 vesicles released per terminal as the amount of Ca 2+ entry increases.