Beta 2-microglobulin (beta 2-M), a marker that is increased in serum during immune activation, was investigated during the course of HIV infection. beta 2-M rose promptly in the first phase of HIV infection in people who were participating in a longitudinal study where serum samples and lymphocyte subset data were obtained at 6-monthly intervals. A rise in beta 2-M level in the first seropositive sample was seen in 93% of 50 HIV seroconverters, and those with high (or low) levels of beta 2-M at the end of year 1 tend to remain high (or low) in the ensuing years. Eighty-three per cent of seroconverters experienced a fall in CD4 T cells in the first year. The magnitude of the CD4 T-cell decline, however, did not correlate with the rise in beta 2-M in specific individuals in the first year. Nevertheless, 2-3 years after seroconversion, the initially increased beta 2-M levels did correlate inversely with the (reduced) level of CD4 T cells (P less than 0.001). Thus, the pattern of disease reflected by beta 2-M level is established in the first year of infection and persists through the following 2 years. beta 2-M levels were found to correlate with rate of CD4 T-cell fall in individuals with established HIV infection. Three groups of HIV-seropositive people with similar CD4 T-cell numbers at the first measurements (about 600-800 x 10(6)/l) but different rates of CD4 T-cell fall over the following 2 years were evaluated by beta 2-M levels. The group with stable CD4 T-cell numbers showed a significantly lower level of beta 2-M than the groups with moderately or rapidly declining CD4 T-cell numbers. Increases in beta 2-M levels during the 2 years of observation were found in people exhibiting a rapid decline in CD4 T cells (about 200 cells/year). The level of beta 2-M appears to be an indicator of HIV activity and of the rate of CD4 T-cell fall.(ABSTRACT TRUNCATED AT 250 WORDS)