The hypothesis that the direction of chromosome segregation in cell hybrids is determined by the interaction of parent cell cycles, or S-phase times, predicts that the segregant parent will always be the one with the longer cycle, or the longer S phase, and that late replicating chromosomes will be more frequently lost. We have tested this hypothesis by studying cell cycle parameters of mouse, Chinese hamster, and platypus parent cells and by observing chromosome loss and replication patterns in hybrids between them. Two types of hybrids have been studied: mouse–hamster hybrids showed gradual segregation, in one or other direction, of 10–60% chromosomes, while rodent–platypus hybrids (which could be selected under conditions optimal for either parent cell) showed rapid and extreme segregation of platypus chromosomes. We found no correlation between the direction of segregation and the relative lengths of parental cycle times, or phase times, nor between sequence of replication and frequency with which segregant chromosomes are lost. We therefore conclude that the direction and extent of segregation is not directly determined by the interaction of parental cycle or phase times.Key words: cell hybrids, chromosome loss, cell cycle, S phase.