Various studies suggest that eukaryotic chromosomes may occupy distinct territories within the nucleus and that chromosomes are tethered to a nuclear matrix. These constraints might limit interchromosomal interactions. We have used a molecular genetic test to investigate whether the chromosomes of Saccharomyces cerevisiae exhibit such territoriality. A chromosomal double-strand break (DSB) can be efficiently repaired by recombination between flanking homologous repeated sequences. We have constructed a strain in which DSBs are delivered simultaneously to both chromosome III and chromosome V by induction of the HO endonuclease. The arrangement of partially duplicated HIS4 and URA3 sequences around each HO recognition site allows the repair of the two DSBs in two alternative ways: (i) the creation of two intrachromosomal deletions or (ii) the formation of a pair of reciprocal translocations. We show that reciprocal translocations are formed approximately as often as the pair of intrachromosomal deletions. Similar results were obtained when one of the target regions was moved from chromosome V to any of three different locations on chromosome XI. These results argue that the broken ends of mitotic chromosomes are free to search the entire genome for appropriate partners; thus, mitotic chromosomes are not functionally confined to isolated domains of the nucleus, at least when chromosomes are broken.