In the present study, genetic crossings were performed between the most TCDD-susceptible (Long-Evans) and the most TCDD-resistant (Han/Wistar) rat strains. The F1 offspring were as resistant to TCDD as the Han/Wistar rats irrespective of the sex of their Han/Wistar parents. In test-cross and F2 progeny the distribution of resistant and susceptible phenotypes was consistent with inheritance regulated by 2 (possibly 3) autosomal genes displaying complete dominance, independent segregation, and an additive co-effect. These data show that, in contrast to earlier findings in mice, TCDD resistance seems to be the dominant trait in the rat. Moreover, the results challenge the current view that the Ah-locus is the exclusive determinant of TCDD sensitivity.