Elevated (greater than 2.2 mg/l) CSF beta-2-microglobulin (beta 2m) level was found in 9 of 16 neurologically symptomatic patients but in only 4 of 21 who were neurologically symptom-free (P less than 0.01). Serum beta 2m concentration was elevated (greater than 2.5 mg/l) in 12 of 16 neurologically symptomatic patients but in only 8 of 21 symptom-free patients (P less than 0.01). When the CSF and serum beta 2m levels were related to various stages of HIV infection, the highest mean values for both CSF and serum were found in patients with acquired immunodeficiency syndrome (AIDS), followed by lower values in AIDS-related complex (ARC), lymphadenopathy syndrome (LAS), and asymptomatic seropositive individuals (ASX), in decreasing order of preference. Our results suggest that elevated beta 2m in CSF and serum is related to the stage of general HIV infection and that elevated CSF beta 2m in the presence of intact BBB may be useful in evaluating CNS involvement in HIV-infected patients.