Two new paired domain genes of Drosophila, Pox meso and Pox neuro, are described. In contrast to the previously isolated paired domain genes, paired and gooseberry, which contain both a paired and a homeo-domain (PHox genes), Pox meso and Pox neuro possess no homeodomain. Evidence suggesting that the new genes encode tissue-specific transcriptional factors and belong to the same regulatory cascade as the other paired domain genes includes (i) tissue-specific expression of Pox meso in the somatic mesoderm and of Pox neuro in the central and peripheral nervous system, (ii) nuclear localization of their proteins, (iii) dependence on prd activity and (iv) presence of the paired domain in genes of known regulatory activity. While no mutant phenotypes of Pox meso and Pox neuro have yet been discovered, a murine gene with a paired domain closely homologous to that of Pox meso has recently been identified with the undulated mutant. Both Pox meso and undulated are expressed in tissues derived from the somatic mesoderm. The five known Drosophila paired domains fall into three classes: (i) the prd,gsb-class, (ii) the Pox meso, undulated-class and (iii) the Pox neuro-class which probably includes the paired domain of the murine gene Pax 2.