Endothelin (ET) is a peptide originally identified as an endothelial-derived vasoconstrictor. It is now recognized that ET is produced by and acts on many other tissues including the brain and spinal cord, where it is believed to modulate neurotransmission. The present studies demonstrate that ET is synthesized by and secreted from postganglionic sympathetic neurons. With the use of Northern analysis, ET-1 mRNA was detected in cultures of sympathetic superior cervical ganglion (SCG) neurons isolated from 3- to 5-day old rat pups. ET-1 and ET-3 peptides were also detected in cultured SCG neurons using immunohistochemistry. ET-1 (50 pg/106 cells) and ET-3 (173 pg/106 cells) were detected by radioimmunoassay of media conditioned by cultured SCG. ET-1 (77 pg/mg protein) and ET-3 (30 pg/mg protein) were also detected by radioimmunoassay of extracts of adult SCG.