It is not clear what determines the outcome of hepatitis B surface antigen (HBsAg) infection, although evidence suggests that the absence of antibody to HBsAg (anti-HBs) is responsible for the development of the carrier state. The synthesis of immunoglobulin G (IgG), anti-HBs and antibody to hepatitis B core antigen (anti-HBc) was measured in pokeweed mitogen-stimulated cultures of peripheral blood mononuclear cells from 12 chronic HBsAg carriers, 5 patients with acute hepatitis B (AHB) during recovery phase and 11 subjects with anti-HBs in serum (controls). All 3 groups showed similar amounts of IgG synthesis. Anti-HBc was detectable in lymphocyte cultures of 10 of 12 chronic HBsAg carriers and 2 of 5 AHB patients, but in none of the controls. Anti-HBs was found in cultures from 6 of 11 controls, and not in carriers or AHB patients. Both in vitro anti-HBc and anti-HBs levels correlated significantly with serum titers of anti-HBc and anti-HBs respectively. B cells from controls cocultured with irradiated (helper) T cells from carriers and AHB patients produced anti-HBs normally. In contrast, B cells from 11 of 12 carriers and 3 of 5 AHB patients cocultured with irradiated control T cells did not synthesize detectable amounts of anti-HBs although they synthesized normal amounts of IgG and anti-HBc. T cells from 8 of 12 carriers and all AHB patients suppressed anti-HBs synthesis by mixtures of control B cells and control irradiated T cells, but these T cells did not affect IgG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)