The recent isolation and characterization of the SALMFamide neuropeptides (S1 and S2) from the starfish Asterias rubens has initiated a series of single- and double-labelling immunocytochemical studies to ascertain their tissue distribution and cellular localization. Specific novel monoclonal and polyclonal antisera have been raised against these neuropeptides and used in optical immunocytochemistry (ICC). The results of the present study reveal, for the first time, the widespread neuronal distribution of S2 localized to axons and perikarya of the radial nerve cord and tube foot ectoneural nerve plexus. Double labelling revealed a predominantly separate localization for S1 and S2 immunoreactivity. The potential functional roles of S1 and S2 in the radial nerve cord (RNC) and tube feet of Asterias rubens are discussed.