Peyronie's disease (PD) is a condition characterized by localized and often progressive fibrosis and scarring of the penis. This condition has an unknown etiology although several hypotheses have been proposed. These include traumatic, immunologic and genetic causes. We studied the genetics and immunology of PD using both molecular biologic and molecular genetic techniques. Men (n=283) with PD were identified by retrospective chart review of one physician's office practice. These men were contacted by telephone and asked to submit to an interview and blood test for genetic studies. Simultaneously, tissue and cells collected in the laboratory were examined by Western and Northern blot analysis for examination of protein and RNA for expression of HLA. Of the first 107 men contacted, 24 were available and consented to interview and blood testing. The mean age was 60.3 y with an average duration of PD of 4.9 y. One patient had a family history of PD while no patients had Dupuytren's contracture. Twenty patients were considered to have primary disease while four were secondary. Eleven patients had tissue prepared for Northern blot analysis and nine patients were the subject of Western blot analysis. All tissue, both Peyronie's and control expressed class I MHC while no tissue expressed class II MHC. The expression of mRNA of class I MHC was equal for Peyronie's and control patients while the expression at the protein level was less in the PD patients. We conclude that PD may have multiple etiologic agents. One cannot exclude a class II MHC association but in our population, HLA DQ is not expressed. Class I MHC may be involved as the expression of class I MHC protein is different in Peyronie's patients than in controls. Genetic studies are ongoing. International Journal of Impotence Research (2000) 12, Suppl 4, S127-S132.