Our understanding of the development of intrinsic reproductive isolation is still largely based on theoretical models and thorough empirical studies on a small number of species. Theory suggests that reproductive isolation develops through accumulation of epistatic genic incompatibilities, also known as Bateson-Dobzhansky-Muller (BDM) incompatibilities. We can detect these from marker transmission ratio distortion (TRD) in hybrid progenies of crosses between species or populations, where TRD is expected to result from selection against heterospecific allele combinations in hybrids. TRD may also manifest itself because of intragenomic conflicts or competition between gametes or zygotes. We studied early stage speciation in Arabidopsis lyrata by investigating patterns of TRD across the genome in F 2 progenies of three reciprocal crosses between four natural populations. We found that the degree of TRD increases with genetic distance between crossed populations, but also that reciprocal progenies may differ substantially in their degree of TRD. Chromosomes AL6 and especially AL1 appear to be involved in many single-and two-locus distortions, but the location and source of TRD vary between crosses and between reciprocal progenies. We also found that the majority of single-and two-locus TRD appears to have a gametic, as opposed to zygotic, origin. Thus, while theory on BDM incompatibilities is typically illustrated with derived nuclear alleles proving incompatible in hybrid zygotes, our results suggest a prominent role for distortions emerging before zygote formation. C OMPLETE reproductive isolation between natural populations is usually achieved through several reproductive barriers, acting at different developmental stages. In plants prezygotic reproductive isolation acts either prepollination (e.g., habitat, temporal, or pollinator isolation) or postpollination (e.g., unilateral incompatibility or conspecific pollen precedence). Postzygotic isolating mechanisms either reduce viability, fertility, or fitness of hybrids or prevent development of a hybrid altogether. The effect of postzygotic reproductive barriers may be environment dependent (e.g., Hatfield and Schluter 1999) or independent of the environment. The latter, intrinsic postzygotic barriers, cause reduced viability or fertility of hybrids and have been studied extensively, e.g., in Drosophila (for a review see Coyne and Orr 2004;Presgraves 2010).Despite the importance of development of reproductive isolation as an evolutionary process, and despite considerable study, precise molecular genetic mechanisms of postzygotic isolation have rarely been described (Presgraves 2010;Rieseberg and Blackman 2010). It is generally assumed, however, that intrinsic postzygotic isolation is due to Bateson-Dobzhansky-Muller incompatibilities (BDMI;Orr 1995;Orr and Turelli 2001). These incompatibilities emerge when in (usually) isolated populations new alleles arise, which upon secondary contact do not function together. In a few cases single genes involved in BD...