Idiopathic hemochromatosis (IH) was considered a rare hereditary disease until population studies in the U.S.A. and Northern Europe indicated an unexpectedly high frequency. In this study we estimated the prevalence of IH in Italy by testing 1301 presumably healthy blood donors. Transferrin saturation (TS) and serum ferritin (SF) levels were used as screening methods. The subjects with TS greater than 50% and/or SF greater than 300 micrograms/l in men and greater than 160 micrograms/l in women were given a complete medical and laboratory examination and those with evidence of iron overload were asked to undergo liver biopsy. Five male donors but no female donors presented increased iron indexes. Diagnosis of homozygous IH in two of them was confirmed by liver biopsy, indicating a prevalence of the disease in this population of 0.2%; that is a gene frequency of 4.5% and a heterozygote frequency of 9%. Since our study might underestimate the true prevalence of the disease because blood donors are at high risk of iron depletion, IH could be one of the most frequent hereditary diseases in Italy. Large-scale screening of young adults based on TS and SF determinations should be proposed for early diagnosis and treatment.