In this study we assessed the chromosomal consequences of double-strand breaks (DSBs) in Saccharomyces cerevisiae under conditions where there was no imposed selection for chromosomal changes. Despite very efficient homologous DSB repair pathways, when we exposed yeast diploids to ionizing radiation doses resulting in about 250 DSBs per cell more than half of the surviving colonies exhibited altered karyotypes. To characterize the specific genome rearrangements observed in radiation survivors, we employed microarray-based Comparative Genomic Hybridization (CGH), which identifies regions of the genome where an imbalance of gene dosage has resulted. Remarkably, the radiation-induced chromosomal alterations appeared to be non-randomly distributed, with the majority of the rearrangements identified in our data set (86%) involving intra- or interchromosomal events between Ty insertions or solo LTRs. Interestingly, specific Ty insertions were found as sites of rearrangements much more frequently than expected. This was the case for a pair Ty1 insertions on the right arm of chromosome V which represented 25% of all Ty-mediated rearrangements. We also identified rearrangements between other homeologous sequences which were not Ty-related (6%), such as a chromosomal translocation between chromosomes IV and V mediated by the HXT15 and HXT13 loci. High levels of instability were also detected at genomic regions containing the ribosomal DNA and CUP1 tandem repeats. To characterize chromosomal aberrations which did not result in a gene dosage change we isolated rearranged chromosomes from pulse-field gels and hybridized this DNA to microarrays. This analysis revealed events which were missed by the CGH analysis, but that were still the result of homologous recombination mediated by Ty-associated sequences. Some of these rearrangements represented an unusual class of recombination products in which two DNA ends (presumably formed by a single DSB) engaged in recombination repair with distinct donor sequences. Taken together, these observations indicate that homologous recombination was the predominant pathway involved in the creation of chromosomal rearrangements, and illustrate the importance that repetitive DNA sequences (i.e. Ty insertions) have in genome dynamics. We suggest that the Ty-mediated rearrangements are due to recombination between homologous elements competing with recombinational repair between sister chromatids or homologous chromosomes.