The Hemochromatosis and Iron Overload Screening Study is a multi-center epidemiological study of the prevalence and genetic and environmental determinants of iron overload and hereditary hemochromatosis in a diverse and representative primary care-based sample of men and women aged 25 and older. Over 101,000 patients undergoing routine screening or testing involving a blood draw were recruited from five Field Centers and screened for transferrin saturation levels. Cost-effective population-based strategies for recruitment was also considered. A repeat fasting transferrin saturation screen in conjunction with a serum ferritin assay was used to identify potential 'case' participants with confirmed elevated transferrin saturation levels and matched random 'control' participants with confirmed non-elevated transferrin saturation levels.