Serum concentrations of beta-2-microglobulin (B2-M) were correlated with disease outcome in 40 children infected by the human immunodeficiency virus. Serum B2-M serum concentrations below 3.0 mg/100 ml or decreasing concentrations were indicative of a stable disease course but were also noted preterminally in lymphopenic children. Of 20 patients with B2-M concentrations above 3.0 mg/liter, 12 had a progressive disease course and 8 remained stable. In the latter 8 patients the B2-M values decreased with time. Elevated B2-M concentrations were also noted in infants younger than 1 year of age and denoted active human immunodeficiency virus infection. B2-M serum concentrations are a useful prognostic marker in human immunodeficiency virus-infected children.