Recombinant human Interleukin-1 Alpha (rhu IL-1 alpha) was assessed for its efficacy in modifying the immunosuppression of mice compromised by Cyclophosphamide (CY), retrovirus infection or surgical stress. Sublethal dose (300 mg/kg) of CY caused neutropenia, decreased cellularity of bone marrow and inhibited Natural Killer (NK) cell activity and lymphokine-activated killer (LAK) cell activity in DBA/2 mice. A single dose of rhu IL-1 alpha (1000 units/per mouse) i.p. accelerated recovery of blood neutrophils and bone marrow cellularity and restored NK and LAK cell activity in CY-treated mice. Mice infected with Friend Virus Complex (FVC) had decreased percentages of L3T4+ cells and a reversed L3T4+/Lyt-2+ ratio; NK and LAK cell activity also decreased. These impaired cellular parameters were restored by rhu IL-1 alpha treatment (1000 units/per mouse/daily i.p. starting on day 5 for 5 days). NK and LAK cell activity was impaired by surgical stress. A single dose of rhu IL-1 alpha (1000 units/per mouse) i.p. 20 hours before transfemoral amputation restored NK and LAK cell activity to normal levels in these mice. These studies indicate that rhu IL-1 alpha possesses immunomodulatory effects in vivo for a broad range of stresses.