We examined the level of postzygotic reproductive isolation in F1 and F2 hybrids of reciprocal crosses between the Arabidopsis lyrata subspecies lyrata (North American) and petraea (European). Our main results are: first, the percentage of fertile pollen was significantly reduced in the F1 and F2 compared to the parental populations. Second, mean pollen fertility differed markedly between reciprocal crosses: 84% in the F2 with ssp. lyrata cytoplasm and 61% in the F2 with ssp. petraea cytoplasm. Third, 17% of the F2 with ssp. petraea cytoplasm showed male sterility (produced less than 30 pollen grains in our subsample). The hybrids were female fertile. We used QTL mapping to find the genomic regions that determine pollen fertility and that restore cytoplasmic male sterility (CMS). In the F2 with ssp. lyrata cytoplasm, an epistatic pair of QTLs was detected. In the reciprocal F2 progeny, four QTLs demonstrated within‐population polymorphism for hybrid male sterility. In addition, in the F2 with ssp. petraea cytoplasm, there was a strong male fertility restorer locus on chromosome 2 where a cluster of CMS restorer gene‐related PPR genes have been found in A. lyrata. Our results underline the importance of cytonuclear interactions in understanding genetics of the early stages of speciation.