Newborn mice of several inbred strains develop few or no tumors following i
noculation with highly tumorigenic strains of polyomavirus. Here we show th
at such resistant strains can be divided into two groups based on the respo
nses of adult mice to radiation followed by virus inoculation. Most strains
show a radiation-sensitive form of resistance (Rr-s) and develop tumors fo
llowing radiation and virus challenge. This type of resistance has previous
ly been recognized as immunological, based on T-cell responses against viru
s-encoded neoantigen(s) expressed in tumor cells. Other strains exhibit a r
adiation-resistant form of resistance (Rr-r) and fail to develop tumors whe
n treated in the same manner. Three additional properties of Rr-r mice dist
inguish them from Rr-s mice: (i) survival of newborns following inoculation
with a highly virulent and usually lethal strain of virus, (ii) resistance
to virus spread in newborns inoculated with either tumorigenic or virulent
virus strains, and (iii) dominant or semidominant transmission of resistan
ce in crosses with a highly susceptible strain. The Rr-r phenotype reflects
a constitutive nonimmunological type of resistance that is targeted to the
virus and blocks its dissemination.