Abstract— A crude particulate fraction, prepared from the central ganglia of Helix or Aplysia, contains levels of adenylate cyclase activity comparable to those in mammalian brain. This activity can be stimulated up to 50-fold by NaF, and 4- to 10-fold by guanyl nucleotides such as GTP and guanylylimidodiphosphate (Gpp(NH)p). A peptide-containing extract from Helix or Aplysia nervous system also stimulates the adenylate cyclase, by 50-400°. In contrast, a number of peptides known to occur in vertebrate and invertebrate nervous system are without effect. The adenylate cylase stimulation by the endogenous molluscan peptide-containing extract may be receptor-mediated, but the effect is not enhanced in the presence of guanyl nucleotides: in this respect it differs from many other hormone-sensitive adenylate cyclases. The endogenous extracts prepared from Helix and Aplysia each stimulate both Helix and Aplysia adenylate cyclases, suggesting that the putative cyclase-linked receptors may be similar in the two species. Furthermore, the active components in the extracts from Helis and Aplysia appear to be similar, since preliminary evidence suggests that they may interact with the same adenylate cyclase-linked receptor in particulate fraction from Helix ganglia.