Sex chromosome dosage compensation in Australian marsupials exhibits several characteristics not ordinarily manifested in eutherian mammals. They are: 1) preferential inactivation of the paternally derived X-chromosome in somatic tissues; 2) a state of partial inactivity at some paternally derived X-linked gene loci in some cells; 3) absence of dosage compensation in some cell types; 4) absence of nuclear sex dimorphism at interphase; 5) discordance between late DNA replication and gene inactivation in some cell types; 6) failure of the X-chromosome to behave as a single unit. Despite these seemingly major differences between the dosage compensation systems of Australian marsupials and eutherians, there are also many underlying similarities. We propose that the two systems arose from a common ancestral mechanism in which the X-chromosome was regulated in a piecemeal fashion, rather than as a whole. To determine more precisely the sequence and timing of evolutionary events, we have initiated an investigation of dosage compensation in American marsupials, which diverged from Australian marsupials soon after the divergence of marsupials from eutherian mammals.