IN its classic form, the hypothesis of X-chromosome inactivation holds that only one of the two X-chromosomes present in cells of female mammals is functional. The "decision" of which X-chromosome is to operate in a cell occurs quite early in embryogenesis and, once made, is irreversible for that cell and all its progeny. The net effect of the inactivation is to make the dosage of X-chromosomal genes (and, therefore, gene products) equal in male and female cells. Despite the apparent general validity of the inactivation hypothesis, it has been recognized from the beginning that certain observations are not easily reconciled . . .