In order to demonstrate possible roles of retrodifferentiation in relapses after differentiation therapies, we have established a retrodifferentiated cell line (RD-1) from a single rat myelomonocytic leukemia cell which differentiated into a macrophage-like cell by treatment with lipopolysaccharide (LPS). The established RD-1 cells showed microscopic features slightly maturer than their parent cells. The RD-1 cells had the ability to differentiate into macrophagelike cells by treatment with fewer doses of LPS than those for parent cells. All rats inoculated with the parent cells (more than 10(2)/rat) died within 50 days. Rats inoculated with 10(4) RD-1 cells survived for more than 120 days, whereas two out of four rats inoculated with 10(5) cells and all the rats inoculated with 5 x 10(5) cells died of leukemia. These results suggest that RD-1 cells are retrodifferentiated cells from a single rat myelomonocytic leukemia cell which differentiated into a macrophage-like cell; they have similar phenotypes and lower tumorigenicity than the parent cells and they also suggest that the appearance of retrodifferentiated leukemia cells may be responsible for relapse after differentiation therapy for leukemia in some cases.