Interest in including screening for hemochromatosis in the routine medical care of adults has grown in recent years. In March 1997, at a meeting on iron overload at the Centers for Disease Control and Prevention, the directors of four hemochromatosis screening programs described the major challenges that they faced and the lessons that they learned in implementing their programs. Seven issues were consistently described as important challenges: 1) changes in case definitions of hemochromatosis, 2) selection of screening threshold values and identification of false-positive cases, 3) variability and lack of standardization in screening test measurements, 4) physician education, 5) informed consent and concerns about medical and genetic discrimination, 6) patient compliance with screening and therapy, and 7) incidental detection of iron deficiency. The two programs that have been completed report a prevalence of iron overload from hemochromatosis of 4.2 to 4.5 per 1000 persons screened; this is consistent with findings in the recent literature. All programs report that screening is feasible and propose that hemochromatosis be defined by repeated elevated serum transferrin saturation values(with or without DNA test results) rather than by the clinical outcome of excessive iron in tissue. The goal of screening programs is to diagnose iron status disorders, particularly hemochromatosis, before they lead to iron overload and chronic disease states. Further research is needed on the ability of genetic and phenotypic tests to predict the clinical expression of hemochromatosis. The experiences outlined in this report highlight practical issues that need to be addressed when iron status screening for hemochromatosis is implemented. It is hoped that this information will facilitate similar efforts in other health care settings.