Recently Feder et al. have identified the gene responsible for hereditary hemochromatosis; it is located 3 Mbp telomeric of the MHC region on chromosome 6p and is called the HFE gene. The majority of the patients with hemochromatosis harbour the same missense mutation, Cys282Tyr. A second missense mutation (His63Asp) of which the significance is less clear, has also been described. To our knowledge the percentage of these two missense mutations in Flemish hemochromatosis patients is not known. Materials and methods: Forty nine (49) unrelated patients with the clinical diagnosis of hemochromatosis were screened for the two missense mutations. The missense mutations were diagnosed with a PCR technique. Results: Of the 49 patients, 46 patients were homozygous for the Cys282Tyr mutation (94%), 2 were heterozygous (4%) and 1 carried two normal alleles (2%). Of the 3 patients not homozygous for the Cys282Tyr mutation, 3 were heterozygous for the His63Asp mutation (2 patients were 'compound heterozygotes'). Discussion: The percentage of homozygotes (Cys282Tyr) in a Flemish hemochromatotic population is comparable with the figures published in the literature. The second missense mutation (His63Asp) could be of importance in association with the Cys282Tyr missense mutation.