Upon characterization of WHSC1, a gene mapping to the Wolf-Hirschhorn syndrome critical region and at its C-terminus similar to the Drosophila ASH1/trithorax group proteins, we identified a novel protein domain designated PWWP domain. To gain insight into its structure, evolutionary conservation and its potential functional role, we performed database searches to identify other PWWP domain-containing proteins. We retrieved 39 proteins, and a multiple alignment shows that the domain spans some 70 amino acids. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position, the composition of amino acids close to the PWWP motif and the pattern of other domains present, we hypothesize that the domain is involved in protein-protein interactions.