The development of chloroleukemia in the rat after transplantion of C51 chloroma cells can be aborted by treatment with an exogenous source of differentiating activity (DA) or by stimulation of endogenous DA production by the administration of Imuvert, a biologic response modifier. Success or failure of treatment was determined by the ratio of DA to leukemic cell load. Accordingly, in the present study we examined the hypothesis that treatment with cytosine arabinoside (ARA-C) to reduce the leukemic cell load coupled with Imuvert would be more effective than either given alone. Treatment with ARA-C-Imuvert aborted the development of chloroleukemia in 79% of the animals in contrast to 0%, 9% and 45% in animals treated with buffer, ARA-C, or Imuvert respectively. These results suggest that stimulation of endogenous DA in combination with cytoreductive agents offers a potentially curative treatment for myelogenous leukemia.