In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation.