This study reports the effects of a combination of azidothymidine (AZT) plus acyclovir (ACV) on both pluripotent (spleen colony-forming units, CFU-S) and committed (granulocyte-macrophage colony-forming units, CFU-GM; erythroid burst-forming units, BFU-E) murine hemopoietic progenitors. Administration of AZT alone was associated with severe hemotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, CFU-S, CFU-GM, and BFU-E. This, however, was followed by a prompt recovery of hemopoiesis. Administration of ACV alone did not modify the hematological parameters studied, whereas the combined administration of AZT and ACV led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with AZT alone. Only the decrease in CFU-S was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of ACV to AZT does not appear to increase the hemotoxicity of the latter.