The presence of actinomycin D during irradiation of HeLa cells leads to radiosensitization under aerobic but not under hypoxic conditions. Depending on the time interval between incubation with the drug and irradiation, pre- or post-treatment with actinomycin D also increases the radiosensitivity of HeLa cells irradiated in air. Pretreatment with actinomycin D does not inhibit recovery from potentially lethal radiation damage. In split-dose experiments, recovery from sublethal radiation damage was not impaired by the drug if present during the entire fractionation interval or if it was given as a short exposure after the first radiation dose.