The distribution of G6PD red blood phenotypes in an unbiased sample of 77 Sardinian certain heterozygotes for the GdMediterranean mutant was found to be skewed in favor of the G6PD (+) cells. Four of these individuals exhibited the normal hemizygous phenotype in all of their cells, but two of them had a mosaic population of G6PD (+) and (-) red blood cells when reexamined after 1 year. These findings suggest that somatic selection may be the main factor determining the phenotype variability of individual somatic cells in highly differentiated tissues of heterozygotes at the G6PD locozygotes for the GdMediterranean mutant should not be used as a criterion for precise estimation of the embryonic or stem tissue cell pool at X inactivation.