The cytogenetic expression of fragile sites is highly variable. Sites are seen in differing proportions of cells. To determine if part of this variability is genetic, the proportions of lymphocytes manifesting the fragile X were examined in a large cohort of males with the fragile X chromosome. The number of fragile X cells was solely determined by genetic factors: the heritability as determined from the correlation between brothers as well as between cousins was 99.6% and 94.4%, respectively, as compared with 0% in unrelated males with the fragile X. This is consistent with pure genetic determination without any environmental influence over the expression of the fragile X chromosome in males.