Genetic susceptibility to chemically induced skin cancer in mice is controlled by multiple unlinked genetic loci. Mus spretus mice have dominant resistance genes which confer resistance to interspecific F-1 hybrids with susceptible Mus musculus strains. We have mapped three major resistance loci using a combination of Mapmaker/QTL analysis and multiple regression analysis to mouse chromosomes 5 and 7. At least two independent loci on chromosome 7 exert their effects primarily during benign tumour development and have very little influence on tumour progression. On the other hand, probably a single locus on chromosome 5 affects both early and late stages of malignancy. The results indicate that benign and malignant tumours are largely under independent genetic control.