The marine jellyfish Podocoryne carnea (Cnidaria, Hydrozoa) has a metagenic life cycle consisting of a larva, a colonial polyp and a free-swimming jellyfish (medusa). To study the function of HOX genes in primitive diploblastic animals we screened a library of P. carnea cDNA using PCR primers derived from the most conserved regions in helix 1 and helix 3 of the homeobox. A novel gene, Cnox2-Pc, has been isolated and characterized. Cnox2-Pc is a HOX cluster-like gene, and its homeodomain shows similarity to the Deformed subfamily of HOM-C/HOX genes. In situ hybridization revealed that Cnox2-Pc is expressed in the anterior region of the larva, the polyp head, and the most apical ectoderm of the differentiating bud during medusa development. In adult medusa expression is restricted to the gastrovascular entoderm. The results suggest that Cnox2-Pc is involved in establishment of an anterior-posterior axis during development in primitive metazoans.