Cytokine and immune activation marker levels in plasma are valuable measurements of immune status and treatment effects in human immunodeficiency virus (HIV) infection and AIDS. Five populations representing various stages of disease were studied: controls, 2 AIDS groups with <50/mm³ CD4 cells, and 2 groups of HIV-positive subjects—1 with stable CD4 T cells (median, 545/mm³) and 1 with >1100/mm³ CD4 cell decline in 1 year. Relatively stable levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (R)II, soluble interleukin-2R, neopterin, and β₂-microglobulin (β₂M) were documented over 5–8 weeks in patients with AIDS and for 1–4 years in the other groups. β₂M was generally the most stable marker. Interferon-γ levels, however, fluctuated substantially. Individuals, whether normal or HIV-positive, maintain characteristic plasma levels of cytokines and immune activation markers. Thus, documented changes, in excess of the variability observed in this study, are likely to be significant indicators of change in disease status or effects of therapy.