Severe weight loss is a common manifestation of advanced infection with the human immunodeficiency virus. The level of tumor necrosis factor alpha (TNF-alpha), an inducer of cachexia in laboratory animals, is elevated in the serum of some patients with AIDS. In a pilot study, five patients with unexplained AIDS-related wasting were treated with pentoxifylline, a known suppressor of TNF-alpha production. Three of the five patients had elevated baseline serum levels of TNF-alpha, and these three patients did not have significant weight gain after 4-8 weeks of pentoxifylline therapy despite the reduction of serum TNF-alpha levels. The remaining two patients, who did not have elevated serum levels of TNF-alpha, continued to lose weight and developed extensive bacterial pneumonia within 3 weeks of starting pentoxifylline therapy. Thus, therapy with pentoxifylline did not clearly benefit the patients with AIDS-related wasting in this uncontrolled pilot study; indeed, it might have been harmful for a subgroup of these patients.