Peripheral T lymphocytes from asymptomatic HBsAg carriers and hepatitis B (HB) immune (naturally acquired or vaccine induced) donors were induced into interleukin-2 (IL-2) secretion by plasma-derived HBsAg and the translational products of the S- and pre-S2+S gene of HB virus (HBV) in vitro. Biphasic time courses of IL-2 secretion were obtained for all donors tested. The first peak seemed to be mitogenically induced, as it was demonstrated in T cell cultures from asymptomatic HBsAg carrier, HB-immune donors as well as HB-susceptible controls and exhibited similar kinetics to that of the mitogen phytohaemagglutinin (PHA) induced IL-2 secretion. The mitogenically induced IL-2 secretion was prompt in T cell cultures from asymptomatic HBsAg carriers compared with HB-immune and HB-susceptible donors, and significantly higher after stimulation with high (100-1,000 ng/ml) compared with low (0.1-1.0 ng/ml) concentrations of HBsAg, indicating that T lymphocytes from asymptomatic HBsAg carriers are mitogenically pre-activated by circulatory HBsAg in high concentrations in vivo. In contrast, the second peak obtained after 4-7 days of antigen stimulation was antigen-specifically induced as it was not registered in control culture supernatants from HB-susceptible individuals. T cells from six out of seven asymptomatic HBsAg carriers exhibited reduced responsiveness to the translational product of the S-gene of HBV, whereas T cells from HB-immune donors responded equally well to pre-S2 containing and non-containing HBsAg preparations. An HBsAg-induced mitogenic T cell activation and aberrant T cell sensitization towards S-gene-encoded determinants may result in altered immunoregulatory functions within the T cell compartment, with consequences for the development of an adequate antibody response to HBsAg in asymptomatic HBsAg carriers.