We have evaluated in vitro the modulating effect of interferon (IFN) alpha, beta and gamma as well as interleukin 2 (IL-2) on the radiosensitivity of large granular lymphocytes (LGL) having natural killer cell activity. LGL were treated with IFNs or IL-2 in concentrations from 1 to 1000 U/ml before or after a single or a split dose of irradiation. The viability of LGL was measured by intracellular ATP, and cytotoxicity by a 51Cr release assay. Both viability and cytotoxicity were clearly higher when IFNs and IL-2 were used before irradiation. Some IFNs were slightly radiosensitizing in ATP studies. Only IFN gamma in a concentration of 1000 U/ml was significantly radioprotective in cytotoxicity tests when used before irradiation. IL-2 had a significant concentration-dependent radioprotective effect in cytotoxicity when used before or after irradiation, and in the viability of preincubated LGL. No combination of IFNs and IL-2 was more radioprotective than IL-2 used alone. IL-2 retarded the time dependent decrease of ATP and 51Cr release levels after irradiation. According to our results, IL-2 is a radioprotective substance for LGL.