My lab has focused on the etilogy of hypospadias. In prospective clinical studies through our PCRC (now CTSI) we have shown that defects in androgen metabolism are a rare form of hypospadias and account for only a tiny minority of patents with hypospadias. We have identified a number of genes in humans that are associated with increased risk of hypospadias. We continue to collect and bank blood, DNA and serum from all our patients with hypospasdias and collaborate with mutlple investigators on genetic projects. We were the first to report on an epigenetic DNA methylation abnormalities as a possible etiology of hypospadias. Finally, we have extensively reviewed the human data on endocrine disruptors as the etilogy of hypospadsias the hypothesis of this proposal.