The interaction of radiation and Adriamycin (ADR) in vivo was studied in 3 different sizes of the EMT6/SF tumor, i.e., 1 cm flank tumors, 2 mm macroscopic lung nodules, and microscopic pulmonary metastases. For the flank tumors the drug was slightly more effective when administered intravenously (IV) than intraperitoneally when survival was assayed in vitro at 24 hours after drug treatment. No significant cell kill or growth delay was observed at doses below 15 mg/kg when the response was assayed with the lung colony assay and regrowth analysis. When ADR was combined with radiation, there was no significant difference in survival with variation of the time interval between drug and radiation administration from -48 hrs. to +48 hrs. When flank tumors were treated with ADR, 15 mg/kg IV, followed in 24 firs. by graded doses of radiation, additive killing effect was seen at low radiation doses but the survival levels were the same as radiation alone at high doses. Adriamycin was slightly more effective against 2 mm artificial macroscopic pulmonary metastases than the flank tumors, but it did not cause significant changes in the radiation dose response curve of these tumors. When the EMT6/SF tumor cells were treated in the lungs 24 hours after transplantation, there was increased cell kill with ADR alone when compared to the 2 mm macroscopic metastases and 1 cm flank tumors. The combined effects of ADR and radiation for the microscopic pulmonary metastases appeared to be strictly additive killing. © 1979.