We have conducted a quantitative analysis of the gangliosides extracted from brain, spleen, thymus, and liver tissue of 8-week-old male mice from H-2 congenic mouse strains on the B10 background, using high performance thin-layer chromatography (HPTLC). An analysis of variance of replicate samples of liver from strains B10, B10.A, and B10.G revealed that the time of sample and colony of origin were not sources of significant variance but that for N-glycolylated gangliosides GM2, GM 1, and GD 1 a, the differences detected between strains were significant. Particularly important were the differences for GM 1: the values of 0.0 % for B 10, 19.0 % for B10.A, and 36.0% for B10.G were each significantly different from the others (P<0.0005). Further studies with liver tissue from B 10/A H-2 recombinant strains also revealed three significantly different levels of GDla: ~<4.0% [B10, B10.A (3R), B10.A (5R), B10.A (18R)], 11.0% (B10.A), and 33% [B10.A (1R), B10.A (2R), B10.A (4R)]. Our findings support prior studies which indicate that a gene linked to the H-2 complex affects hepatic GM2 galactosyltransferase activity. However, they also indicate that the current model, which classifies all strains as possessing either an allele for "high" enzyme activity or a single alternative allele for "low" enzyme activity, is probably oversimplified, since at least three levels of enzyme activity appear to exist as stable phenotypic markers. Moreover, the current model cannot readily account for the three different levels of GD l a observed with B 10/A H-2 recombinants. Alternative models are proposed, including the novel suggestion that a distinct H-2 linked gene may affect hepatic GM 1 sialyltransferase activity. These findings demonstrate that further study of H-2 linked genes affecting the activities of glycosyltransferases is indicated.