The present study is concerned with an opioid system in the human trematode Schistosoma mansoni, both as part of the endogenous chemical messenger system and as a tool in the parasite reaction to the host(s). A high-affinity opioid binding site was characterized in membrane suspensions prepared from adult worms. Scatchard analysis revealed a single class of receptors with a dissociation constant of 1.8 nM and a Bmax of 24.9 pmol/g protein for (D-Ala2, Met5)-enkephalin (DAME). The displacement experiments demonstrated that the most potent ligands were beta-endorphin, DAME, and met-enkephalin. These characteristics and the effects of various ions on DAME affinity suggest that S. mansoni has a delta-like opioid receptor, as previously described in other invertebrates. A met-enkephalin-like peptide was also characterized in a miracidial extract. Radioimmunoassay, reverse-phase HPLC, and bioassay by induction of cell conformational changes of human polymorphonuclear leukocytes revealed that the parasite peptide is very similar to authentic met-enkephalin. A met-enkephalin-like peptide was also shown to be present in adult worms and in their incubation medium. Taken together, these observations demonstrate the existence of a complete opiate system in S. mansoni. We discuss its role in molecular signaling within the parasite and in host-parasite interactions.