We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.