During our study of the DDK syndrome, we observed sex ratio distortion in favor of males among the offspring of F(1) backcrosses between the C57BL/6 and DDK strains. We also observed significant and reproducible transmission ratio distortion in favor of the inheritance of DDK alleles at loci on chromosome X among female offspring but not among male offspring in (C57BL/6 x DDK)F(1) x C57BL/6 and (C57BL/6-Pgk1(a) x DDK)F(1) x C57BL/6 backcrosses. The observed transmission ratio distortion is maximum at DXMit210 in the central region of chromosome X and decreases progressively at proximal and distal loci, in a manner consistent with the predictions of a single distorted locus model. DXMit210 is closely linked to two distortion-controlling loci (Dcsx1 and Dcsx2) described previously in interspecific backcrosses. Our analysis suggests that the female-offspring-specific transmission ratio distortion we observe is likely to be the result of the death of embryos of particular genotypic combinations. In addition, we confirm the previous suggestion that the transmission ratio distortion observed on chromosome X in interspecific backcrosses is also the result of loss of embryos.