Neurotransmitter regulation of the siphon and adjacent mantle region of bivalves has not previously been examined. In the biofouling bivalve, Dreissena polymorpha, acetylcholine and FMRFamide both elicited contractions of siphon/mantle preparations. Hexamethonium bromide inhibited acetylcholine-elicited contractions but had no effect on FMRFamide-elicited contractions. FMRFamide-like immunoreactivity and chromatographic evidence for acetylcholine were found in central ganglia and the siphon/mantle region. Extracts of siphons, gonads, and gills, separated on Sephadex G-25, also contained macromolecules larger than acetylcholine and FMRFamide that caused siphon/mantle contraction. These results demonstrate regulation of contraction by several potential neurotransmitter agents in a new bivalve preparation, the siphon/mantle.