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Objective: To perform a cost-benefit analysis of screening for hereditary hemochromatosis., Patients and Methods: A total of 3,977 consecutive men > or = 30 years of age who presented for routine health checkups at a health maintenance organization medical center were screened for hereditary hemochromatosis by measuring transferrin saturation. Subjects with repeated transferrin saturation > or = 62% and ferritin level > or = 500 ng/mL (> or = 500 micrograms/L) were referred for liver biopsy. Subjects with transferrin saturation < 15% were referred for evaluation. Laboratory testing, screening, and abnormal screening test evaluation procedures were identified by chart review., Results: Forty patients had transferrin saturation > or = 62%. One hundred seventy-two had transferrin saturation < 15%. Eight patients with hemochromatosis were identified. The 3 patients most seriously affected had hepatic iron concentrations > 250 mumol/g dry weight. Two of them had hepatic fibrosis. Seven cases of hemochromatosis were found among 1,974 white subjects who were screened. Only 1 case was found among the remaining subjects., Conclusions: Our observations support routine screening with transferrin saturation for white men > or = 30 years of age.