Plasma HIV-1 RNA and CD4(+) T-cell counts after HIV-1 seroconversion are important independent markers that predict the clinical course of I-W-I infection. The prognostic significance of these parameters during primary HIV-1 infection, however, remains largely unknown. In a cohort of 53 male study subjects (age, 33 +/- 7 years), who consecutively presented with primary HIV-I infection, we analyzed the relationship between early plasma HIV-1 RNA, CD4(+) and CD8(+) T-cell counts, beta(2)-microglobulin, and p24-antigen levels determined in the first 3 months and subsequent plasma HIV-1 RNA levels and CD4(+) T-cell counts 6 to 12 months after onset of primary symptoms. Peak, nadir, and median HN-1 RNA levels in the first 30 days were already significantly associated with HIV-I RNA levels at 6 to 12 months (p = .02, p <.0001, and p = .01, respectively). Similarly, early nadir and median CD4(+) T-lymphocyte counts in the first 30 days showed a significant relationship with CD4(+) T-cell counts at 6 to 12 months (p = .009 and p = .0008, respectively). Study subjects with an early decline of CD4(+) counts to <500 cells/mu l had an eightfold higher risk that CD4(+) counts were <500 cells/mu l at I year. Of all evaluated virologic parameters, only nadir HIV-I RNA at 76 days predicted CD4(+) counts at 6 to 12 months (p = .006). Early HIV-1 RNA levels and CD4(+) counts are already associated with the time course of those parameters 6 to 12 months after onset of symptoms. Nadir viral load was the strongest predictor of HIV-I RNA levels as well as of CD4(+) counts at 6 to 12 months. An early decline of CD4(+) T lymphocytes may be a useful clinical prognostic marker for rapid disease progression.