Genes of the Polycomb and trithorax groups (PcG and trxG) are part of a cellular memory system that maintains inactive and active states of homeotic gene expression in Drosophila. Recent genetic evidence indicates that several related loci in mammals are also involved in the regulation of Hox genes. Like their Drosophila counterparts, the vertebrate gene products are components of multiprotein complexes that regulate transcriptional activation, repression and aspects of chromatin structure. Initial indications suggest the existence of a large mammalian PcG and trxG family, with a potential to encode multiple specialised functions in cell fate and cell-cycle control.