In a Japanese family several members in three generations had, on hemoglobin analysis, typical findings of heterozygous beta-thalassemia. However, hemoglobin concentrations, red cell morphology, splenic size and clinical histories indicated that the disorder was more severe than in the usual beta-thalassemia trait. From the previous and the present studies folic acid supplements appeared to be beneficial in ameliorating the anemia. The findings may provide an apparent pathophysiologic and genetic explanations for the more severe anemia and red-cell abnormalities present in a small proportion of families with beta-thalassemia trait.