In an earlier publication we described similarities at the primary sequence level between the first probable plant G-protein coupled receptor (GPCR) and three GPCR families (families A, B and F according to Kolakowski's classification) that were previously considered evolutionarily unrelated. Here we analyze further the relatedness among different GPCR families. By using PSI-BLAST, which is a search algorithm that is more potent in detecting weak similarities, one finds additional similarities between GPCR families that have not previously been described. Based on these comparisons, it is possible to divide all the GPCR families into one large clade and two smaller ones. The large clade includes the rhodopsin family (family A), the glucagon receptor family (family B), cyclic AMP receptors (family F), an Arabidopsis thaliana receptor, the Frizzled family and probably also the STE3 pheromone receptors (family E) and vomeronasal receptors type 1. The smaller clades consist of, in one case, BOSS and the GABA-B family of receptors (family C), and in the other the STE2 pheromone receptors (family D) alone. Although our findings are likely to reflect a common ancestry within each of these clades, whether or not two or all three of the clades also share an even more ancient ancestor between them remains an open question that cannot be answered from our present data.