The nondisjunction of artificial yeast minichromosomes (2:0 segregation events) during mitosis is accompanied by the appearance of cells containing more than one copy of the minichromosome. A mathematical simulation of this process has demonstrated that under certain conditions, a nondisjunction of the minichromosomes may result in their accumulation in a considerable portion of the cell population. An increase in the copy number of artificial minichromosomes as a result of impaired segregation has been used to develop a new experimental procedure for directly selecting yeast mutants showing an impaired segregation of artificial minichromosomes during mitosis. Four new genes, AMC1, AMC2, AMC3, and AMC4, which control the segregation of artificial minichromosomes in mitosis, have been identified (AMC3 and AMC4 are mapped to chromosome IV and VII, respectively). Mutations in the genes AMC1-AMC4 also affect the mitotic transmission of natural chromosomes. We suggest that the genes AMC1, AMC2, AMC3, and AMC4 control the segregation of natural chromosomes in yeast.