To date no nuclear receptors have been identified or cloned from the phylogenetically oldest metazoan phylum, the Porifera (sponges). We show that retinoic acid causes tissue regression in intact individuals of the demosponge Suberites domuncula and in primmorphs, special three-dimensional cell aggregates. Primmorphs were cultivated on a galectin/poly-L-lysine matrix in order to induce canal formation. In the presence of 1 or 50 micromol l(-1) retinoic acid these canals undergo regression, a process that is reversible. We also cloned the cDNA from S. domuncula encoding the retinoid X receptor (RXR), which displays the two motifs of nuclear hormone receptors, the ligand-binding and the DNA-binding domains, and performed phylogenetic analyses of this receptor. RXR expression undergoes strong upregulation in response to treatment with retinoic acid, whereas the expression of the sponge caspase is not increased. The gene encoding the LIM homeodomain protein was found to be strongly upregulated in response to retinoic acid treatment. These data indicate that the RXR and its ligand retinoic acid play a role in the control of morphogenetic events in sponges.