Incubation of Chinese hamster ovary cells with etanidazole under hypoxic conditions increases cell killing by subsequent treatment with melphalan under aerobic conditions. We report here that this sensitization can be achieved even if periods of hypoxia are interrupted by reoxygenation. Preincubation under hypoxia in the absence of etanidazole also results in sensitization to melphalan. Intermittent hypoxia is less effective than continuous hypoxia as a single sensitizing factor. Glutathione depletion does not appear to have more than an additive effect on chemosensitization by etanidazole. These results suggest that prolonged treatment with low doses of etanidazole may be a more effective strategy for clinical chemosensitization than a short exposure to a higher dose, in order to target intermittently as well as chronically hypoxic cells.