The Polycomb group (PcG) genes in Drosophila melanogaster are required for maintenance of correct spatial expression of homeotic genes, and their products are thought to form either a regulatory network or act as a multimeric complex. Recently, it has been suggested that because of homology between Polycomb (Pc) and Su(var)205, PcG genes encode chromatin proteins required for the maintenance of a determined state in chromatin. The polyhomeotic (ph) gene is a member of the PcG of genes. We present DNA sequence of a ph cDNA, which encodes a 169-kD protein with a single putative zinc finger, a serine/threonine-rich region, and has glutamine repeats, suggesting that ph is a DNA-binding protein. Polyclonal antisera directed against ph protein bind to approximately 80 sites on polytene chromosomes. Most of these sites appear to be the same as those recognized by antibodies to Pc protein. ph protein binds to insertion sites of constructs containing DNA from the bithoraxoid (bxd) region of the Bithorax complex, showing that ph binding to chromatin is DNA dependent. The same bxd constructs are recognized by Pc protein, strongly supporting the hypothesis that ph and Pc interact directly.