The recent availability of the full Saccharomyces cerevisiae genome offers a perfect opportunity for revising the number of homologues to human disease-related proteins. We carried out automatic analysis of the complete S, cerevisiae genome and of the set of human disease-related proteins as identified in the SwissProt sequence data base. We identified 285 yeast proteins similar to 155 human disease-related proteins, including 239 possible cases of human-yeast direct functional equivalence (orthology). Of these, 40 cases are suggested as new, previously undiscovered relationships. Four of them are particularly interesting, since the yeast sequence is the most phylogenetically distant member of the protein family, including proteins related to diseases such as phenylketonuria, lupus erythematosus, Norum and fish eve disease and Wiskott-Aldrich syndrome. (C) 1998 Federation of European Biochemical Societies.