It is now apparent that a proportion of individuals (5-8 %) remains clinically free of HIV-1 disease with normal levels of CD4(+) lymphocytes (greater than or equal to 500/mu l) for more than 8 years following infection, However, the proportion of these individuals who ultimately progress to AIDS remains to be established, We determined the virological and immunological characteristics of a cohort of long-term nonprogressors in Australia and examined the role of these factors in predicting disease progression, Individuals with documented asymptomatic HIV-1 infection for at least 8 years with CD4(+) lymphocyte counts >500 cells/mu l were recruited from hospital clinics and general practices serving the eastern area of Australia, CD4(+) lymphocyte count, rate of CD4(+) lymphocyte change, CD8(+) lymphocyte count, beta(2)-microglobulin, immune complex dissociated (TCD) HIV-1 p24 antigen, and plasma HIV-1 RNA were measured at baseline and multiple visits at B-month intervals over an average period of 2 years, Up to November 1996, 67 study participants were recruited, of whom 72% had been infected with HIV-1 for at least 10 years, HIV-1 RNA correlated with beta 2-microglobulin, ICD p24 antigen, and the ability to isolate virus in culture but not with levels of CD4(+) or CD8(+) lymphocytes. Serum beta(2)-microglobulin was a stronger predictor of CD4(+) lymphocyte decline than HIV-1 RNA and the only factor significantly associated with CD4(+) lymphocyte decline, These findings show that the serum concentration of beta(2)-microglobulin is a strong predictor of immunological progression in people with long-term asymptomatic HIV-1 infection and provides additional prognostic information to HIV-1 RNA in determining the risk of disease progression.