Cells of strain L-P59 of the mouse multiply to at least twice as many cells as those of two L-P59 derivatives, strains Amy and Barbara. In mixed populations with an initially equal proportion of either L-P59 and Amy or L-P59 and Barbara cells, L-P59 cells completely dominated within 4 to 8 weeks. A marker chromosome, known as “D,” was one of the most conspicuous elements in cells of L-P59. Cells contained 0, 1, 2, and 3 D chromosomes. In young cultures, mitotic cells with 0 or 1 D chromosome dominated the population, whereas in aged cultures those with 2 or 3 D chromosomes dominated it. When cultures of L-P59 were subcultured twice a week, the populations shifted to a lower D chromosome content (average D chromosome per cell below unity). Conversely, when cultures were subcultured once in 2 weeks without intervening feeding, the population shifted to a higher D chromosome content (average D chromosome per cell above 1.5). Also, when a young culture was suddenly treated with aged medium, the D chromosome content also increased among the mitotic cells. The results demonstrate that cell populations are composed of numerous genomes which are harmoniously balanced. Under one environmental condition, one or several genomes become the stem cells, but other genomes are able to replace them whenever conditions change.