CCR5 cell-surface expression was studied in relation to CCR5 genotype and clinical course of HIV-1 infection. HIV-1 infected CCR5(+/+) individuals had higher percentages of CCR5-expressing CD4(+) T cells as compared with HIV-l-infected CCR5(32/+). individuals. For both genotypic groups, the percentages of CCR5-expressing cells were higher than for the uninfected counterparts CCR5(+/+), HIV+ 28% and HIV- 15% (p < 0.0001); CCR5(32/+), HIVS. 21% and HIV- 10% (p = 0.001), respectively). In HIV-l-infected individuals, high percentages of CCRS-expressing cells were associated with low CD4(+) T cell numbers (p = 0.001), high, viral RNA load in serum (p = 0.016), and low T cell function (p = 0.053). As compared with nonprogressors with similar CD4(+) T cell numbers, individuals who did progress to AIDS had a higher percentage of CCR5-expressing CD4(+) T cells (32% vs 21% (p = 0.001). Longitudinal analysis of CCRSf/' individuals revealed slight, although not statistically significant, increases in CCRS-expressing CD4(+) T cells and CD4(+) T cell subsets characterized by the expression of CD45 isoforms, during the course of HIV-1 infection. Preseroconversion, the percentage of CCR5-expressing CD4(+) T cells was higher in individuals who subsequently developed AIDS (28%) than in those who did not show disease progression within a similar time frame (20%;p = 0.059), Our data indicate that CCR5 expression increases with progression of disease, possibly as a consequence of continuous immune activation associated with HIV-1 infection, In turn, CCR5 expression may influence the clinical course of infection.