The role of B cells in the pathogenesis of hepatitis B virus (HBV) infection has not been explored in depth. In the present study, the activation status of B cells from peripheral blood of healthy controls (N = 20) and patients with acute hepatitis B (AHB, N = 15) or chronic hepatitis B (CHB, N = 30) was evaluated by measuring the expression levels of B-cell activation markers CD69 and CD86, using quantitative real-time PCR and flow cytometry. Moreover, the potential mechanism underlying B-cell activation during HBV infection was further investigated by analyzing the expression profile of FCRL1, an intrinsic activation molecule of B cells. An elevation in the levels of B-cell activation markers including CD69 and CD86 was observed in the AHB patients (44.31 +/- 9.27, 27.64 +/- 9.26%) compared to CHB patients (30.35 +/- 11.27, 18.41 +/- 6.56%, P < 0.05), which was still higher than healthy controls (12.23 +/- 7.84, 8.22 +/- 3.43%, P < 0.05). Furthermore, the expression of FCRL1 was found to be similar to B- cell activation markers, which was highest in AHB patients (70.15 +/- 17.11%), lowest in healthy donors (36.32 +/- 9.98%, P < 0.05) and half-way between these levels in patients with CHB (55.17 +/- 12.03%, P < 0.05). The results were positively associated with aberrant B-cell activation. These data suggest that B cells can play a role in HBV infection, and therefore more effort should be devoted to exploring their functions.