Pax genes play an important role in networks of transcription factors that determine organogenesis, notably the development of sensory organs. Other members of this regulatory network include transcription factors encoded by the Six gene family. Sponges lack organs and a nervous system, possibly because they have not evolved a Pax/Six network. Here we show that the demosponge Chalinula loosanoffi encodes only one Pax and one Six gene, representatives of the PaxB and Six1/2 subfamilies. Analysis of their temporal transcription patterns during development shows no correlation of their mRNA levels while their spatial patterns show some overlap of expression in adult tissue, although cellular resolution was not achieved. These results do not suggest that these genes form a major network in this basal phylum, although its existence in a minor fraction of cells is not excluded. We further show that sponge PaxB can substitute for some of the Pax2, but not of the Pax6 functions in Drosophila. Finally, we have analyzed the phylogeny of Pax and Six genes and have derived a model of the evolution of the Pax gene subfamilies in metazoans. It illustrates a diversification of Pax genes into subfamilies mostly in triploblasts before the protostome-deuterostome split, whereas few subfamilies were lost in various phyla after the Cambrian explosion.