1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ET. 4. Endothelin promotes the survival of cultured post-ganglionic sympathetic neurons and modulates the morphological and biochemical differentiation of these neurons. 5. Endothelin enhances the activity of nerve growth factor and modulates the release of neurotransmitter from post-ganglionic sympathetic nerve terminals.