Ten to 17% of American couples currently seek medical help for infertility; half of these problems have a male cause usually of unknown etiology. Wildlife, experimental animal and human epidemiological studies indicate that environmental contaminants, especially organochlorine compounds (OCs) such as polychlorinated biphenyls (PCBs) and OC pesticides have adverse effects on male reproduction. To investigate the relationship between measure of human male reproductive health, specifically semen quality and reproductive hormone levels (FSH, LH, testosterone and inhibin B, considered to be the best available endocrine marker of spermatogenesis), OC environmental contaminants and polymorphisms in genes involved in contaminant and sex steroid metabolism (P450), we propose to conduct a case-control study recruiting subjects based on sperm density from an infertility in Detroit, Michigan. Cases will be men with low sperm densities (less than 2 x10x6/ml), and controls (2 groups) will be men with sperm densities greater than 2 but less than 20x10x6/ml, and men with normal sperm densities (greater than 20x10x6/ml). Information on Great Lakes sport-caught fish consumption, as well as on other risk factors will be obtained from a self-administered questionnaire. Secondary exposures (contaminants present in Great Lakes fish), including PCBs and OC pesticides will be measured from a blood sample. P450 polymorphisms will be measured in buccal (cheek) cell DNA. This adequately powered case-control study of men with low sperm densities from an area of the Great Lakes with both known OC contamination and a significant percentage of anglers will provide data that will help determine if consumption of Great Lakes sports-caught fish has or does not have adverse effects on measures of male reproductive health.