Two dominant mutations in the agouti locus of the mouse, viable yellow, Avy, and lethal yellow, Ay, are associated with increased susceptibility to spontaneous as well as virally or chemically induced tumors. Regardless of the mechanism of initiation, this effect is dependent upon the presence of initiated cells. Although complex, the numerous physiologic alterations associated with these mutations offer an interesting model for the study of endogenous promotion. To date, it has been reported that these genes enhance the growth and early appearance of tumors in all organ sites wherein initiated cells exist, suggesting that the system was pan-promoting. In our current study, however, neither Avy nor Ay enhanced the appearance of chemically induced thymic lymphomas in two mouse strains of differing susceptibility. Thus, the concept of a pan-promoting effect is not valid. However, the presence of Ay did enhance the appearance of chemically induced hepatocellular tumors as has been reported previously for Avy. This striking difference of thymomas from other carcinogenic sequences may make possible a better understanding of the nature of susceptibility to endogenous promoting factors.