We have examined the location of the DAZL protein in fetal and adult rodents and human specimens and found that there is a shift from a predominantly nuclear to a predominantly cytoplasmic distribution of the protein in human testis. In rat testis and human ovary, however, the protein is predominantly, if not exclusively, cytoplasmic throughout germ cell development. One possible explanation for this could be that the DAZ protein is responsible for the nuclear localization of DAZL in human males. We have tested this hypothesis by examining the testis of marmosets, which lack the Daz genes and have found that the DAZL protein is both nuclear and cytoplasmic in spermatogonia, and by analyzing testis sections from DAZ-deleted patients in whom the cytoplasmic location of DAZL is evident in remaining germ cells. Transfection experiments indicate that the differences in DAZL expression between rodents and humans are not caused by the amino acid differences between the 2 proteins, and that DAZL is a cytoplasmic protein per se. Variations in location seem to be independent of the presence of the DAZ protein are species specific and, as in Drosophila, may not have great functional significance.