Upregulation of tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of several inflammatory conditions, including rheumatoid arthritis. Therapeutic agents such as antibodies or soluble TNF-alpha receptor analogs, which block TNF-alpha activity are a recent addition to the therapeutic armamentarium for the conditions. We describe a patient who developed aplastic anemia complicated by sepsis after receiving etanercept, a TNF-alpha receptor analog, for the treatment of rheumatoid arthritis. Pancytopenia resolved within 3 wk of discontinuing etanercept. To our knowledge, this is the first report of aplastic anemia associated with TNF-alpha blockade.