Characterizing the genetic and molecular basis of hybrid incompatibilities is a first step toward understanding their evolutionary origins. We fine mapped the nuclear restorer (Rf ) of cytoplasm-dependent anther sterility in Mimulus hybrids by identifying and targeting regions of the Mimulus guttatus genome containing large numbers of candidate pentatricopeptide repeat genes (PPRs). The single Mendelian locus Rf was first isolated to a 1.3-cM region on linkage group 7 that spans the genome's largest cluster of PPRs, then split into two tightly linked loci (Rf1 and Rf2) by <10 recombination events in a large (N = 6153) fine-mapping population. Progeny testing of fertile recombinants demonstrated that a dominant M. guttatus allele at each Rf locus was sufficient to restore fertility. Each Rf locus spans a physical region containing numerous PPRs with high homology to each other, suggesting recent tandem duplication or transposition. Furthermore, these PPRs have higher homology to restorers in distantly related taxa (petunia and rice) than to PPRs elsewhere in the Mimulus genome. These results suggest that the cytoplasmic male sterility (CMS)-PPR interaction is highly conserved across flowering plants. In addition, given our theoretical understanding of cytonuclear coevolution, the finding that hybrid CMS results from interactions between a chimeric mitochondrial transcript that is modified by Rf loci identified as PPRs is consistent with a history of selfish mitochondrial evolution and compensatory nuclear coevolution within M. guttatus.