It is postulated that release of SP from peripheral terminals of sensory neurons contributes to neurogenic inflammation and possibly mediates, in part, the inflammatory response in a variety of diseases. This review addresses the Ca2+-dependent release of SP from peripheral nerve terminals in response to antidromic electrical stimulation of peripheral nerves and noxious thermal and chemical stimuli. Initial studies suggested that SP release is induced via an axon reflex, which involves antidromic impulses travelling along the peripheral nerve terminal. Further investigation indicated that SP release is also induced via direct depolarization of the terminals and, possibly, via a chemically-mediated mechanism which is independent of electrical excitation. Multiple transduction mechanisms, involved in SP release, seem to differ depending on the type of stimulus. These multiple mechanisms may account for the different routes of Ca2+ influx, which occurs via both voltage-dependent calcium channels and receptor-operated channels. It is also emerging that SP release is modulated by endogenous factors which either enhance or inhibit release, making it apparent that the mechanism(s) underlying the release of SP from peripheral nerve terminals is more complex than initially proposed.