Tumor necrosis factor (TNF) and HIV P24 antigen levels were determined in the serum of intravenous drug abusers (IVDAs), homosexuals, and patients with lymphadenopathy or acquired immune deficiency syndrome (AIDS). The mean TNF level in the serum of normal controls was 12 ± 5 compared to 112 ± 25 pg/ml in the serum of HIV-seronegative asymptomatic IVDAs. This increase of TNF may be due to the variety of infections that these people are exposed to persistently. The mean TNF level in the serum of HIV-seropositive asymptomatic IVDAs was 112 ± 79 pg/ml, 31 ± 24 pg/ml in lymphadenopathy, and 55 ± 19 pg/ml in patients with AIDS. The mean P24 level in the serum of patients with AIDS was 50 ± 13 pg/ml compared to 0 pg/ml in HIV-seronegative subjects, while the other HIV-seropositive groups had relatively low levels. The P24 antigen levels may reflect viral load in these patients. SIL-2R and p2-microglobulin levels were also elevated in patients with HIV infection. The TNF may play a role in the antiviral activity against HIV virus and in the development of full-blown disease after HIV infection.