Studies were undertaken to determine whether induction of antibody to hepatitis B surface antigen (anti-HBs) production by cultured lymphocytes which had been conducted with pokeweed mitogen (PWM) could be replaced by interleukin 2 (IL 2). In cultures stimulated with purified HBsAg and IL 2, the comparable levels of anti-HBs production to those obtained in cultures stimulated with PWM alone occurred when peripheral blood mononuclear cells (PBMC) from patients positive for serum anti-HBs and recipients of HBsAg vaccine were used as effector cells. Detectable amounts of anti-HBs were produced only when IL 2 was added to the second-set cultures again. IL 2 or HBsAg alone, however, did not induce anti-HBs production. Anti-HBs production was not observed by the additions of these additives when PBMC from chronic HBsAg carriers and control individuals were used. These findings indicate that IL 2 could modulate the immune response to HBsAg.