Combination of actinomycin D and irradiation of the upper portion of the abdomen of dogs in doses which by themselves produce no significant clinical, histologic, or biochemical abnormalities may result in death of the animals. Factorial analysis of crypt-cell data demonstrated a statistically significant independent effect for actinomycin and radiation (p = 0.001). An actinomycin-radiation interaction was not demonstrated, and it is thus proposed that increased effects observed in this investigation were due to simple additivity of the effects of actinomycin and radiation. Mortality appeared related not only to total actinomycin and radiation dose, but also to daily radiation exposure.