Chickens of Regional Poultry Research Laboratory (RPRL) inbred line 63 regress sarcomas induced by Bryan high-titer Rous sarcoma virus to a greater extent than chickens of line 72, although these lines are identical for the major histocompatibility complex (MHC, B complex). They differ, however, at two independent autosomal loci, Ly-4 and Th-1, which determine surface alloantigens of partly overlapping subsets of T lymphocytes. Association of genotypes at these loci with quantitative variation in ability to regress Rous sarcomas was tested in segregating progeny derived from crosses of lines 63 and 72. In the F4 generation chickens of the Ly-4a/Ly-4 a, Th-U/Th-U genotype (symbolized aa/aa) had significantly higher regressor ability than any of the other three double homozygous genotypes. In F5, all nine genotypes formed by combinations of homozygotes and heterozygotes were tested, and higher regressor ability was shown by the aa/aa, ab/aa, and aa/ab genotypes. These results indicate that higher regression is associated with: (1) interaction between the line 63 Ly-4 ~ and Th-1 a alleles in homozygous form; and (2) dominance x dominance interaction, in that the a allele at each locus is dominant for higher regression only within the homozygous aa genotype at the other locus.