G-protein-coupled (seven-transmembrane segment)-receptors represent a major group of metazoan receptors, involved in transduction of extracellular signals. The G-proteins, which are made up of Galpha/beta/gamma-subunits, link the receptors to the effector system(s). To analyze the phylogenetic relationships among the metazoan alpha-subunits of G-proteins, cDNAs of alpha-subunits were isolated from Geodia cydonium, a marine sponge belonging to the lowest metazoan phylum, Porifera. One encodes a putative isotype of a stimulator of the adenylyl cyclase (Galpha s), another one a putative inhibitor of the adenylyl cyclase (Galpha i/o) and the third one a putative activator of phospholipase C (Galpha q). In addition one putative beta-subunit was cloned from the same species. The deduced amino acid sequences of the sponge Galpha s -(putative Mr 44749), the Galpha i/o -(Mr 41064) and the Galpha q subunits (Mr 41363) were found to display high similarity with the corresponding sequences from higher Metazoa, and are only distantly related to those of slime mold, yeast or plants. Of lower similarity are the sequences of the beta-subunits among animals and plants, thus not allowing robust grouping. These data demonstrate that the phylogenetic relationships, obtained from analyses of the alpha subunits from metazoan G-proteins, support the conclusion that all metazoan phyla, including the Porifera are of monophyletic origin.