We investigated the effects of mitogenic stimulation on the cytotoxicity and mutagenicity of X-rays and ethylnitrosourea (ENU) in human peripheral blood lymphocytes using a cloning technique. Resistance to 6-thioguanine (TG) served as the genetic marker. Day 0 (unstimulated) lymphocytes were about two times more radiosensitive than day 3 (stimulated) lymphocytes to the cytotoxicity when compared for the D0 value (0.72 Gy vs. 1.54 Gy), and about five times more radiosensitive to its mutagenicity when compared for the frequency of TG-resistant cells following exposure to 4 Gy of X-rays (25.5 x 10(-6) vs. 126.0 x 10(-6). On the other hand, day 3 (stimulated) lymphocytes were about three times more sensitive to ENU with a D37 value of 1.03 mM compared with 2.82 mM for day 0 (unstimulated) lymphocytes, but as sensitive as day 0 lymphocytes to its mutagenic effect. These results indicate that the sensitivity of lymphocytes for cytotoxicity and mutagenicity is modified by mitogen stimulation, when lymphocytes are exposed to carcinogens or mutagens in vitro.