The influence of adriamycin and adriamycin-radiation combinations on posttreatment proliferative activity of the mouse jejunum was examined by measuring [3H]thymidine incorporation. Single doses of 5 or 10 mg/kg produced a transient reduction in the proliferative activity, while 1 mg/kg had little effect. After 10 mg/kg, there was a rapid decrease in the number of mitotic figures, followed by a gradual decrease in the number of and rate of DNA synthesis in S-phase cells. A compensatory epithelial hyperplasia characterized by an enlarged crypt proliferative population and shortened mitotic cycle duration was observed beginning 48 hr after treatment. Multiple doses of adriamycin totalling 10 mg/kg inhibited cell production to a greater extent than the equivalent single dose. In combination with 1000 R, adriamycin (5 mg/kg) given from 96 hr before to 72 hr after irradiation reduced the amount of postirradiation proliferation.