Unexpected, spontaneous conversion of a family of rats, from low-leukemic to high-leukemic inbred line. From a nucleus of Sprague-Dawley rats received in 1960 from the National Institutes of Health, we have raised, by brother-to-sister mating, a colony of these animals. The incidence of leukemia in 313 females and 316 males was 1.6% and 1.2%, respectively. About 3 years ago, we observed a relatively high incidence of leukemia in offspring of a healthy female, no. 1. Among the offspring of this female, observed through 12 successive generations, there were 17 leukemias among 44 females (38.6%) and 21 leukemias among 40 males (52.5%), developing at ages varying from 6 to 11.6 months. The most frequent form of leukemia observed was acute myeloid, with a high count of myeloblasts, promyelocytes, and myelocytes; lymphatic form was relatively rare but was observed occasionally; pronounced anemia was common. In most instances, on autopsy, the pathological picture was that of an enlarged spleen and liver, with the exception of those few animals that developed lymphatic leukemia, with thymic and mesenteric lymphoid tumors. We have no satisfactory explanation for this sudden, unexpected conversion of a part of our Sprague-Dawley rat colony from low-leukemic to high-leukemic inbred line. As a working hypothesis, the possibility of a spontaneous activation of a hypothetical oncogenic virus should be considered. The high leukemic C58 inbred line of mice originated in a similar, unexplained manner [MacDowell, E.C. & Richter, M.N. (1935) Arch. Pathol. 20, 709-724]. However, leukemia developing in mice was subsequently found to be caused by a transmissible virus, whereas, thus far at least, no evidence of a transmissible virus has been found in leukemia developing spontaneously in rats. 