Hereditary hemochromatosis (HH) is the most common inherited disorder among Caucasians with an estimated frequency as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and develop progressive accumulation of tissue iron stores with consequent organ dysfunction including hepatic cirrhosis, diabetes mellitus, congestive heart failure, arthropathy and impotence. Early diagnosis and institution of phlebotomy treatments will prevent disease manifestations and normalize life expectancy. HH is therefore a natural target for the development of a routine screening strategy. We have already demonstrated the favorable cost-effectiveness ratio of adopting such a screening strategy among thirty year old Caucasian males.(1) However, several important questions remain to be answered before general recommendations regarding screening for HH can be made to primary care practitioners. First, we need to validate our model by confirming disease prevalence among Caucasian males in the primary care setting. Second, prevalence rates need to be determined for females, for other races, and for different age groups in order to determine who should be screened for the disease and at what age. Thirdly, an optimal screening strategy needs to be developed that will identify affected individuals without too many false positive results and will avoid unnecessary invasive procedures. This strategy may vary depending on age, sex and race. Finally, the incidence of subclinical disease manifestations among individuals identified by screening and the risk of developing disease manifestations over the life times of these individuals need to be clarified. The answers to these questions will enable us to determine with greater confidence the relative effectiveness of a screening strategy for HH and will clarify for primary care practitioners which of their patients should be screened for this disorder.