There is growing evidence that neurotransmitters can be released not only by exocytosis but also through the membrane carriers responsible for transmitter reuptake. Giulio Levi and Maurizio Raiteri review the in vitro and in vivo evidence supporting the existence of a carrier-mediated release for different classes of transmitters. While the physiological significance of carrier-mediated release remains speculative, widely used drugs such as sympathomimetic amines, the anorectic drug fenfluramine and some drugs of abuse act in part by stimulating monoamine carrier-mediated release. Moreover, antidepressants known to inhibit monoamine reuptake, can block carrier-mediated release. This mechanism may also come into play in pathological conditions such as ischaemia.