Peripheral blood mononuclear cells (PBMCs) from 70 patients with chronic hepatitis B and 32 normal healthy persons were isolated and cultured with or without Staphylococcus aureus enterotoxin B (SEB; 0.2 mg x l(-1)) and recombinant HBcAg (rHBcAg; 1.0 mg x l(-1)) for 48 h in vitro. After incubation, the cells were harvested by centrifugation and apoptosis of the PBMCs was studied by staining with fluorescent dyes YOPRO-1 and Hoechst 33342. The levels of IL-12 and IL-10 in the serum and the supernatants of cultured PBMCs were assayed by ELISA. The levels of IL-12 heterodimer in the serum and the supernatants of PBMCs cultured with SEB or rHBcAg were lower in patients than controls. The levels of IL-10 in both the serum and supernatants were higher in patients than controls. In addition, the percentage of apoptotic cells in PBMCs from the infected patients was significantly greater than from normal persons in the presence or absence of SEB and rHBcAg. Patients seropositive for HBeAg had much greater percentage of apoptotic cells in the PBMCs cultured with rHBcAg than patients seronegative for HBeAg, reaching 24.08%. We speculate that activation-induced cell death of PBMCs in the patients with hepatitis B may be related to abnormal expression of IL-12 heterodimer and IL-10, which may lead to persistent infection in the patients.