Abstract The cell cycles and chromosome replication patterns of three mouse X Chinese hamster somatic hybrids were compared to those of the parent cells in order to examine whether nucleus-limited factors are involved in the regulation of the cell cycle. DNA synthesis was observed to be initiated synchronously in mouse and hamster chromosome sets, but terminated earlier in the latter set. The length of the S period was equal to that of the mouse parent (which had the longer S phase), and did not change with time after hybridization. The terminal pattern of DNA synthesis among hamster chromosomes appeared to be similar in hamster and hybrid cells. Therefore, as in heterokaryons, the activities of the two complements in hybrids are synchronized at mitosis, and at the beginning of the S period, but the rate and pattern of DNA synthesis appears to be regulated autonomously. The G1 and G2 periods of hybrids were initially very long, but became reduced with time in culture. These long gap periods, together with the observation that hamster as well as mouse chromosomes were frequently lost from hybrid clones, argues against the hypothesis that preferential chromosome loss results from the overlapping of DNA synthesis and mitosis.