Mice with the recessive hereditary disease, Hertwig's anemia (an/an), exhibit a persistent mild macrocytic anemia and reduced fertility. We examined mitotic figures from bone marrow and kidney cells of adult mice and from liver cells of fetal mice that were genetically normal or had Hertwig's anemia. Uniformly normal mitotic figures were observed in the nonanemic mice (+/+ or +/an). In contrast, 5% to 15% of the mitotic figures were abnormal in mice homozyous for Hertwig's anemia (an/an). These aberrant cells were hyperploid, containing more than the normal complement of c40 chromosomes, but fewer than 80 chromosomes. Cells with abnormal numbers of chromosomes may show decreased viability or proliferative capacity. The occurrence of such abnormal cells in an/an mice could explain (1) the loss of progenitor stem cells during erythroid maturation, resulting in an anemic phenotype; and (2) the depletion of germ cells during ontogeny, resulting in reduced fertility.