Six patients with high-risk acute myeloid leukemia (AML) relapsing after allogeneic bone marrow transplantation (BMT) were treated with interferon-alpha 2b to stimulate graft-versus-leukemia reactions. Additionally, donor mononuclear cells were infused with or without interleukin-2 as first-line treatment or upon failure of interferon-alpha 2b in 5 patients. Two patients developed clinical acute graft-versus-host disease (GVHD) after a combination of donor leukocytes and interferon-alpha, and one developed de novo chronic GVHD after interleukin-2 and interferon-alpha. Complete remission was attained in 4 patients whereas 2 patients showed no response. Two of the responding patients relapsed rapidly. Four patients died of a combination of complications of immunotherapy and progressive disease. Two patients are alive in remission with chronic GVHD (Karnofsky performance scores of 80%) 8 and 18 months after immunotherapy. We conclude that cytokine-mediated immunotherapy with or without donor cell infusions may be effective in some cases of AML relapsing after allogeneic BMT, and may result in long-term survival. With limited data, it appears that development of chronic GVHD after immunotherapy is essential for continued remission.