C57BL/10(H-2b) and A/J(H-2a) mice have different phenotypes as to the age dependent changes in the expression of GM1 and GD1a in the liver, i.e., the contents of these two components in total gangliosides in C57BL/10 and A/J mice were 1 and 20% at 4 wk and had decreased to almost 0 and 10%, respectively, at 8 wk [Y. Nakamura et al. (1988) J. Biochem. 103, 393-396]. To analyze the mode of inheritance of these phenotypes, C57BL/10 mice were mated with A/J or A/Wy(H-2a) mice. The phenotype of A/J or A/Wy mice was found to be inherited by the F1 hybrids, indicating that the phenotype of A mice is dominant over that of C57BL/10 mice. The (C57BL/10 x A/Wy)F1 hybrids were then backcrossed with one of the parent strains, C57BL/10 mice. The phenotype of A/Wy mice was demonstrated to be inherited by 23 out of 35 mice and all of the 23 had the H-2a haplotype. These results suggest that the two phenotypes of C57BL/10 and A mice are controlled by a pair of allelic genes on a locus which is closely linked to the H-2 complex on chromosome 17. Unexpectedly, B10. A(H-2a) mice were found to have significantly higher amounts of GM1 and GD1a than both C57BL/10 and A mice, although they were a H-2 congenic strain carrying the H-2 genes transferred from A/Wy mice and should have the same genes on loci next to H-2 as one of the two strains. It remains to be determined how B10.A mice have higher amounts of GM1 and GD1a than C57BL/10 and A/Wy mice.