Development of tongue carcinoma (TC) in rats by 4-nitroquinoline 1-oxide (4NQO), a potent carcinogen, is under host genetic control. The inbred Dark-Agouti (DA) strain rats showed a much higher susceptibility to TC than the Wistar-Furth (WF) strain. The author's previous study on crosses between two strains postulated a susceptibility gene in DA and a resistance gene in WF rats. This hypothesis was confirmed by the genetic analysis of the backcrosses to either parent and F2 with a simple sequence repeat polymorphism analysis. In the crosses between the DA and WF strains of rats, two major independently segregating host loci that influenced the cancer development by application of 4NQO positively or negatively were identified and mapped. DA rats had a semidominant susceptibility gene, Stc1, closely linked with D19Mit9 on chromosome 19, which was on the segment syntenic to human chromosome 16. In contrast, WF rats had a semidominant resistance gene, Rtc1, closely linked with D1Rat320 on chromosome 1, which is syntenic to human chromosome 11. The presence of other susceptibility and resistance genes on some chromosomes of both DA and WF rats was suspected, and they will be clarified in the near future. These findings provide powerful evidence that chemically induced tongue carcinogenesis is a multigenetic event.