Normal mice and mice with advanced Rauscher leukemia were given a single dose of HU (0.5 mg/g body wt) and evaluated for the effect of the drug on splenic CFU-S 4 and 16 hr later. Exposure to HU reduced the total number of CFU-S for both normal and leukemic mice by 50% at 4 hr. At 16 hr there was no recovery in CFU-S evident in the normal mouse. However, CFU-S levels in the spleens of the leukemic mice had recovered to nearly that existent before exposure to HU. Effects of HU on total splenic mass differed from that on the CFU-S. Recovery of total splenic mass was seen to have begun in normal animals by 16 hr after HU, while in the leukemic animals spleen size had receded further by 16 hr. The data suggest that, as in man, the hematopoietic recovery responses following exposure to chemotherapeutic drugs may be significantly different in Rauscher viral leukemic mice as compared to normal mice. The possible applicability of Rauscher leukemia as a model for leukemia therapy studies is briefly discussed. © 1980, SAGE Publications. All rights reserved.