Sensitivity of a library of cloned adenovirus-transformed rat cell lines of varying tumorigenicity to cytotoxic action of tumor necrosis factor alpha (TNF alpha) was studied and correlated with their sensitivity to NK/LAK cell cytolysis. Our data confirm earlier reports that expression of the E1A oncogene of Ad2 or Ad5 is associated with sensitivity of transformed cells to TNF alpha and also NK/LAK cytotoxicity. Ad2-transformed cell line which expresses the E3 early region in addition to the E1 gene block is resistant to TNF alpha, but remains sensitive to NK/LAK cells. All cell lines which express the E1A oncogene of highly oncogenic Ad12 are resistant to NK but not LAK cells. Their sensitivity to TNF alpha, however, varies over a broad range and does not correlate with either their susceptibility to NK/LAK cytolysis or their tumorigenic potential.