The effects of split low-dose total-body irradiation (TBI; 150 cGy) on production of interferon (IFN)-gamma and Interleukin-2 (IL-2) and on the growth characteristics of erythroid progenitor cells (BFU-E) have been assessed in normal mice, normal mice receiving TBI only, mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P), and FVC-P infected mice receiving 150 cGy TBI on days 5 and 12. It was found that lymphocytes from the spleens of TBI-treated mice previously infected with FVC-P produced in response to phytohemagglutinin (PHA) and concanavalin A (Con A) stimulation up to 15 times greater amounts of IFN-gamma than cells from untreated FVC-P-infected mice. IL-2 production in Con A-stimulated spleen cell cultures also increased when cells were isolated from FVC-P-infected mice treated by low-dose TBI compared to untreated FVC-P-infected mice. TBI treatment was associated with greater than 99% ablation of "erythropoietin-independent" BFU-E colony formation. The results suggest that the cure of FVC-P-infected mice by low-dose TBI may result from activation of the IFN-gamma system and IL-2 production.