Iron overload in Africa was previously regarded as purely due to excessive iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated iron binding capacity may be influenced by an interaction between dietary iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated iron binding capacity after supplementation with vitamin C. For each measure of iron status, segregation analysis was consistent with an interaction between a postulated iron-loading gene and dietary iron content (P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 micrograms/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 micrograms/L in an unaffected individual with identical age, sex, and beer consumption. This segregation analysis provides further evidence for a genetic influence on iron overload in Africans.