The amino acid composition and pI values were calculated for the predicted proteins of a series of complete poxvirus genomes. Many of the vaccinia virus (strain Copenhagen) minor ORFs, thought not to be functional genes, were found to have significantly more or less of several amino acids than a set of the largest 150 vaccinia virus proteins. Very high isoelectric point (pI) values were also correlated with a group of the minor ORFs. Analysis of molluscum contagiosum virus ORFs by amino acid composition and pI identified a number of ORFs previously denoted as doubtful and highlighted several others that could be similarly classified. The use of amino acid composition and pI appears to be a generally applicable tool to aid identification of viral ORFs that are unlikely to be functional genes.