AIM: To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus (HBV) replication in different clinical stages of chronic HBV infection.METHODS: A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages: immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time polymerase chain reaction.RESULTS: CD8± T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages (36.87 ± 7.58 vs 34.37± 9.07, 36.87± 7.58 vs 28.09 ± 5.64, P < 0.001). The peripheral blood in patients at the immune-tolerant and immune active stages contained 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P < 0.01),whereas the peripheral blood in patients at the immuneinactive carrier stage and in normal controls contained less CD8+ T-cells than CD4+ T-cells (28.09 ± 5.64 vs 36.85 ± 6.06, 24.02 ± 4.35 vs 38.94 ±3.39, P < 0.01).ANOVA linear trend test showed that CD8+ T-cells were significantly increased in patients with a high viral load 5.71, P < 0.001), while CD4+ T-cells were significantlyincreased in patients with a low HBV DNA load (37.45 ±6.14, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P< 0.001). Multiple regression analysis displayed that logcopies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3+, CD4+ and CD8+ cells and CD4+/CD8+ ratio after adjustment for age at HBV-infection, maternal HBV-infection status,presence of hepatitis B e antigen and HBV mutation.CONCLUSION: Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.