Immunologic prevention of the carcinogenicity of the diagnostic gamma-emitting radionuclide 99mTechnetium (99mTc) by lymphotoxin was evaluated using an in vivo-in vitro assay of carcinogenesis. Pregnant Syrian golden hamsters received 125-2,300 microCi 99mTc/kg body weight by injection, and 7 days later colonies of morphologically transformed cells were quantitated in vitro. The transformation frequency increased directly with the radionuclide concentration, and cells derived from transformed colonies produced tumors in athymic nude mice. The total absorbed 99mTc dose was 0.20 rad following injection of 250 microCi 99mTc/kg hamster body weight; this compares with an exposure of 0.13 rad following injection of 143 microCi 99mTc/kg body weight in humans. Intravenous injection of purified hamster lymphotoxin immediately after 99mTc caused a dose-dependent reduction in the transformation frequency. Transformation was essentially completely prevented (97%) by injection of 8,000 U of lymphotoxin. Thus, the immune system, through the action of lymphotoxin, has the potential to prevent carcinogenesis induced by gamma-radiation from 99mTc. This emphasizes the importance of considering the recipient's immune and other homeostatic mechanisms as part of a complete diagnostic or therapeutic gamma-radiation regimen.