Actinomycin D was administered intravenously to 13 children with inoperable cancer. Of eight children who received the agent alone, two experienced regression of tumor, of whom one had Wilms' tumor and the other rhabdomyosarcoma. Of five children who received the drug in association with radiation therapy, two had beneficial responses, which were apparently due to the Actinomycin D rather than to radiation. One of these children had rhabdomyosarcoma and the other a sarcoma of the mesentery. Toxic manifestations consisted of nausea and emesis, oral ulcerations, depression of hematopoiesis, diarrhea, and alopecia, in that order of frequency. The changes in the skin associated with x-radiation appeared to become exaggerated after therapy with Actinomycin D. The estimated optimal dosage for children is 2.4 mg/m2 of body surface area. This amount produced benefit or mild oral toxicity without causing significant depression of the bone marrow. Lower doses are advised during second courses and for patients who have had prior therapy with bone marrow depressants or who have impaired renal function. Further investigation of the usefulness of Actinomycin D alone and in combination with ionizing radiation in the treatment of cancer seems indicated.