We report a new type of non-deletional hereditary persistence of fetal hemoglobin that is due to a C-->T transition at position -158, relative to the Cap site of the human Agamma-globin gene. This mutation was identified in three unrelated adult cases presenting slightly elevated levels of fetal hemoglobin (Hb F), i.e. 2.9-5.1%, and normal hematological indices. Our sequencing results, from both polymerase chain reaction-amplified and subcloned DNA fragments, indicate that the A gamma -158C-->T mutation occurred by two independent gene conversion events in the three cases studied. In addition, hematological and molecular data, including restriction fragment length polymorphism haplotyping in the beta-globin gene cluster, extended haplotype analysis inside the gamma-globin gene region and routine analysis of three tandem repeat loci (D1S80, 3'HVR/apoB and F8vWf), led us to conclude that the A gamma -158C-->T mutation in one of the three cases occurred recently in the parental germ line (P=99.47%), representing the first example of a de novo gene conversion event identified in humans.