Evidence is presented that LDH virus infection of mice results in drastic changes in several immune activities. Serum IFN titer and splenic NK activity are increased during the acute phase of infection. NK stimulation is mediated by IFN-alpha,beta since injection of an antibody against murine IFN-alpha,beta is able to abolish the effect. IL-2 production is inhibited throughout the study period following injection of LDH virus (14 days), although a partial recovery is observed during the second week. Similarly, IL-2 receptor expression and MLC responsiveness are suppressed. This suppression lasts for 2 and 7 days respectively after injection. Addition of recombinant IL-2, but not of indomethacin, to the MLC cultures restores the proliferation rate. Not only proliferation but also cytotoxic cell generation in MLC is diminished during the first week after LDH virus injection. Again, this response is normalized at day 14. Additional observations indicate that LDH virus is present in murine neuroblastoma. This explains some of the previously described effects of this tumor on the cellular immune system of the host.