Three mutations have recently been detected in the hereditary hemochromatosis HFE gene (282C-->Y, 63H-->D, and 65S-->C). To determine their prevalence in a northeastern Spanish Mediterranean population, we studied 812 subjects between 18 and 75 years of age, randomly selected from the electoral roll of three villages. There were no homozygotes for the 282C-->Y or S65D mutations in this sample. For the 63H-->D mutation, 4.8% were homozygotes; 4.3, 32.3, and 2% were heterozygotes for the 282C-->Y, 63H-->D, and 65S-->C mutations, respectively. The prevalence of compound heterozygotes was 2% for 282C-->Y/63H-->D and 0.6% for 63H-->D /65S-->C. We found no significant differences between men and women. In conclusion, 46% of this Mediterranean population of Spain are carriers of at least one of the three mutations that can increase iron absorption.