Using genome screen, DNA sequence and mapping data, we scanned the human chromosomal region 17q21-q24 for polymorphic markers in single copy genes. Three such genes were identified: the gene for myeloperoxidase (MPO) at 17q21.3-q23.2, containing a CA-microsatellite in the eighth intron and a functional single base substitution (G to A) in the promoter region, the platelet endothelial cell adhesion molecule-1 gene (PECAM1) at 17q23, which has a CA-repeat sequence in the sixth intron, and the gene for the regulatory subunit RIalpha of cAMP-dependent protein kinase (PRKAR1A) at 17q23-q24, in which a GA-microsatellite was detected in the 5'-flanking region. Association of these polymorphisms with multiple sclerosis (MS) was studied in a Swedish case-control population of 199 MS patients and 145 control subjects, and in 203 simplex families from Sardinia. None of these polymorphic genes was found to be a genetic marker for disease susceptibility. These results are in contrast with previous studies on the involvement of MPO in MS and suggest that the elevated expression of PECAM-1 in MS, as earlier documented, is related to transactivation by other gene products.