Radiation dose-response assays were performed for 2 tumors; the endpoint was the mean radiation dose yielding local tumor control in 50% of animals (TCD50). Injection of vitamin A after local irradiation of an antigenic fibrosarcoma in normal animals gave a 15–20% reduction in TCD50. There was no effect of vitamin A after irradiation of the fibrosarcoma in immune-suppressed animals or against a mammary carcinoma of very weak antigenicity. The TCD50 for the fibrosarcoma in mice actively sensitized to this tumor before transplantation was higher than in unsensitized animals, which suggested immunological enhancement; in such mice, injection of vitamin A after local irradiation reduced the TCD50 by 25%. The effect of vitamin A on radiation response of 2 normal tissues was assayed. Surviving fraction of intestinal crypt cells and the acute reaction of skin were the same in vitamin A and saline-injected mice exposed to a single dose of radiation. Administration of vitamin A had no effect on TD50 (i.e., the mean number of tumor cells required to generate tumors in 50% of animals) when a simple suspension of fibrosarcoma cells was injected into normal mice. However, the drug abolished the growth-enhancing effect observed when lethally irradiated cells were admixed with the standard cell suspension. After irradiation of an antigenic tumor, radiation-damaged cells prior to their lysis may compete with surviving cells for a limited immune-rejection response. We suggest that vitamin A acts mainly by increasing the rate of lysis of damaged cells, thus concentrating the immune response against cells surviving irradiation, but that it may also directly stimulate the immune-rejection response in animals sensitized to their tumors before transplantation.