NGIWYamide, a neuropeptide recently isolated from sea cucumbers, was tested on tube feet of the starfish Asterina pectinifera. NGIWYamide (10⁻⁶–10⁻⁴ M) caused contraction of isolated tube feet. NGIWYamide-like immunoreactivity (NGIWYa-LI) was investigated with an antiserum against NGIW-Yamide. NGIWYa-LI was found in the radial nerve cord (RNC), the marginal nerve, and the tube feet. Both ectoneural and hyponeural parts of the RNC showed NGIWYa-LI. Immunoreactive cell bodies were found in both parts of RNC. Extensive labeling in the basal region of the ectoneural part suggests that a substantial proportion of axons in this part contains NGIWYamide or a similar substance. In tube feet, NGIWYa-LI was found in the sub-epithelial nerve plexus and in the basal nerve ring. Double labeling along with 1E11, a neuron-specific monoclonal antibody developed from A. pectinifera, indicated that the structures with NGIWYa-LI are neurons. These results suggest that NGIWYamide or an NGIWYamide-like peptide exists in starfish and functions as a neurotransmitter or a neuromodulator.