Serum beta 2-microglobulin (beta 2M) levels were measured by radioimmunoassay in 962 unmarried men recruited by probability sampling from areas in San Francisco, Calif, most severely affected by the epidemic of acquired immunodeficiency syndrome (AIDS). From July 1984 to December 1987, 65 incident AIDS cases occurred in 388 homosexual/bisexual men infected by the human immunodeficiency virus (HIV) at the time of recruitment. The mean level of beta 2M in uninfected individuals at entry was 170 nmol/L. In HIV-seropositive patients who had not developed AIDS, the mean beta 2M level was 254 nmol/L, and in those who had developed AIDS, the beta 2M level was 347 nmol/L. After 36 months of follow-up, 34% of individuals with beta 2M levels greater than 322 nmol/L at entry developed AIDS, 21% of individuals with levels between 246 and 322 nmol/L developed AIDS, while only 7.3% of those with levels below 246 nmol/L developed AIDS. The beta 2M level predicted the development of AIDS independently of the CD4 lymphocyte count in HIV-seropositive individuals. Thus, 65.5% of HIV-seropositive individuals with beta 2M levels above 322 nmol/L and CD4 lymphocyte counts of below 500/microL developed AIDS in 3 years. This represents an 18.4-fold increased relative hazard at 3 years over individuals with beta 2M and CD4 cell counts within the reference range for uninfected individuals. A nomogram is provided that allows the easy calculation of the probability of an HIV-infected person developing AIDS in 36 months depending on prevalent levels of CD4 lymphocytes and serum beta 2M.