Myosuppressins are a family of the FMRFamide-like peptides. They have been characterized in many insects and shown to inhibit visceral muscle contraction. Rhodnius prolixus possesses an unusual myosuppressin in that the typical FLRFamide C-terminal motif is unique and ends with FMRFamide. In the present study, we isolated the cDNA sequence for the R. prolixus receptor for this unusual myosuppressin (RhoprMSR). Quantitative PCR indicates high relative transcript expression of RhoprMSR in the central nervous system and also supports the previously described physiological effects of RhoprMS on the digestive system, with expression of the RhoprMSR transcript in the midgut and hindgut. Expression of the RhoprMSR transcript was also found in the female and male reproductive system of 5th instar nymphs, with transcript expression greater in the female reproductive tissues. No expression was found in the salivary glands or Malpighian tubules. A functional receptor expression assay confirmed that the cloned RhoprMSR is indeed activated by RhoprMS (half maximum effective concentration = 42.7 nM). Structure-activity studies based upon both functional receptor assays and physiological assays showed the importance of the HVFMRFamide moiety, as further N-terminal truncation removed all activity.