Mammalian cells (V79-379A) in suspension culture rendered chronically hypoxic showed greater resistance to Adriamycin than exponentially growing aerobic cells. Resistance to Adriamycin increased as a function of the time cells were held under hypoxic conditions, with maximal resistance after 6 h. Chronically hypoxic cells retained their resistance when reoxygenated, and did not return to their original sensitivity until they had been in air for 24 h. Uptake of Adriamycin was similar for chronically hypoxic and exponentially growing aerobic cells, but much more than for plateau-phase cells. These findings suggest that chronically hypoxic cells in tumours may be resistant to this drug.