Venoms of the marine cone snails (Conus spp.) consist of numerous proteins and peptides showing a wide variety of biological activities such as on ion-channels and receptors. Peptides acting on neuronal nicotinic acetylcholine receptors belong to several peptide superfamilies including the recently described αD-conopeptides which are homodimers of identical peptides with 47-49 amino acids. Among the venom glands of 27 Conus species analyzed by cDNA cloning, precursors of αD-conopeptides were identified in four species only: C. betulinus, C. capitaneus, C. mustelinus, and C. vexillum. Phylogenetic analysis of the relationships among the αD-conopeptides revealed that they belong to clades, which are characterized by an AVV- and EMM-motif in the signal peptide sequence.