The ability of the anabolic steroid nandrolone decanoate (ND) to increase megakaryocytopoiesis (MP) and the hematopoietic-inductive microenvironment (HIM) after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation (2 Gy) and on the next 2 days, mice were injected with 1.25 mg of ND in propylene glycol intraperitoneally. Irradiated control mice received only vehicle. Compared to controls, drug-treated mice showed a 151 % increase in the platelet level on day 14. Drug-treated mice also demonstrated a significant rebound in MP, as colony-forming progenitor stem cells (CFU-Mk) from bone marrow rose to 288% of control by day 8 and from spleen to 599% by day 1 following the last drug injection. In addition, drug-treated mice produced a 286% increase in bone marrow and a 378% in splenic stromal cell colonies on day 5 following drug treatment. These results demonstrate that ND enhances MP and HIM following sublethal irradiation. After hemapoietic suppression, ND may serve to stimulate MP and HIM recovery both at the stem cell level and in peripheral blood.