Split low dose total-body irradiation (TBI) with 150 cGy was assessed for its efficacy in modifying the disease induced in DBA/2 mice by the polycythemia-inducing strain of the Friend virus complex (FVC-P, composed of a Friend murine leukemia helper virus and a spleen focus-forming virus). All FVC-P injected mice were dead within 40 days; however, infected mice receiving TBI on days 5 and 12 exhibited long-term survival. FVC-P-injected mice receiving TBI treatment on days 5 and 12 had normal leukocyte counts, normal spleen weights, and no detectable spleen focus-forming virus. Although the FVC-P-infected mice had decreased proportions of L3T4+ cells and increased proportions of Lyt-2+ cells, these were returned to normal following TBI treatment. Apparently the time sequence of TBI treatments is important since one treatment with TBI on day 5, or two treatments with TBI on days 12 and 18, was not as efficacious. The inability of in vitro irradiation doses of up to 1000 cGy to inactivate FVC-P which was subsequently injected into murine hosts suggests that the effectiveness of the TBI treatment in vivo is not due to a direct radiation effect on the virus. These results indicate a possible relationship between L3T4+ and Lyt-2+ numbers or their ratio in the curative efficacy of TBI in FVC-P-infected mice.