Abstract We report the genetic pattern of F 1 hybrid resistance to a panel of tumors of C57Bl/6 origin. All five virally and four chemically induced lymphomas and one of two methylcholanthrene-induced sarcomas tested showed similar patterns with high resistance to small subcutaneous tumor inocula in F 1 hybrids derived from outcrossing C57Bl/6 to strains A, DBA/2, CBA, C3H and A.CA. Analysis of the take incidence in segregating backcrosses and H-2 congenic mice indicated a linkage between resistance and the MHC complex of the partner strain used for the outcross. With the exception of one sarcoma, the H-2 b homozygous hybrids ( B6 × A.BY) and ( B6 × C57L) were as susceptible to all tumors as the homozygous strain of origin. The ( B6 × A.SW) hybrid was significantly more susceptible to some of the lymphomas than the B6 strain. This may be due to an H-2 s -linked dominant susceptibility (suppressor?) gene or a gene dosage effect that would lead to a decrease of relative resistance compared to the syngeneic host. One of the two chemically induced sarcomas studied, MC57X, gave an exceptional pattern. All F 1 hybrid genotypes tested, including the H-2 b homozygotes, showed considerable resistance to this tumor. Backcross tests concurred in confirming that resistance was largely due to non- H-2-linked genes.