The yeast SIR2 gene is involved in regulating nucleosome phasing and transcription in the mating type system. We have found that SIR2 also plays another important role in the cell. Specifically, in wild-type SIR2 strains recombination between the tandemly repeated ribosomal RNA genes is depressed. In sir2 mutants, both mitotic and meiotic intrachromosomal recombination increase 10- to 15-fold. In striking contrast to its effect on rDNA, the SIR2 gene does not affect intrachromosomal recombination between non-rDNA gene duplications. Furthermore, in the absence of the SIR2 gene product, rDNA acquires a partial dependency on recombination gene functions (RAD50 and RAD52) that are normally dispensable for exchange in the rDNA array. Thus, SIR2 may function in excluding the rDNA region from the general recombination system. Here we demonstrate that SIR2's effect is not restricted to controlling mating type expression, but rather that SIR2 functions in a more general way in the genome.