Eight patients who were carriers of beta-thalassemia induced by the cd121 (G-->T) mutation are described in four nonrelated Dutch families. This mutant, which is considered rare and inherited in a dominant manner, is expressed in a different way among each of the four families and even among carriers of the same family. The symptoms vary from an hemolytic anemia of intermediate gravity with hepatosplenomegaly, inclusion bodies and erythroblastosis, to a mild anemia with minor hematological abnormalities. We report the analytical procedures used for the detection of the mutant, the hematological and clinical data of the four families and discuss the variable physiopathology of this molecular defect. We also compare the variation in fetal hemoglobin expression in relation to the haplotypes of the beta-gene cluster and to the different hematological conditions. The presence of this rare mutant in four nonrelated Dutch families could derive from a single mutation or from multiple events. The existence of the four mutations in three different haplotypes suggests the occurrence of at least two independent events. The presence of five abnormal hemoglobins and the beta-thalassemia defect on different haplotypes at cd121 also suggests a relatively increased rate of mutations at this particular site.