The influence of IL-2 and IL-4 on the mitogen-induced immunoglobulin E and IgG production in vitro was analysed. Furthermore the expression of Fc epsilon RII (CD23 antigen), as well as the release of its soluble products, the isotype-specific IgE binding factors (IgE-BF), was determined. Recombinant IL-2 (rIL-2) exerted opposite effects on the synthesis of IgE by human lymphocytes that were stimulated either by pokeweed mitogen (PWM) or Staphylococcus aureus Cowan I (SAC). rIL-2 induced a dose-dependent suppression of IgE and IgG synthesis in the presence of PWM. This effect was accompanied by a significant decrease of IgE-binding factor (BF), whereas the expression of Fc epsilon RII was not significantly modulated by rIL-2. A marked increase of IgE production was observed when lymphocytes, prestimulated with SAC for 48 hr, were further incubated with increasing amounts of rIL-2 for 6 days. In contrast, IL-4 in concentrations ranging from 500 to 4.9 U/ml did not lead to an enhancement of IgE synthesis in lymphocytes that were prestimulated with SAC. However, SAC-induced IgG secretion was significantly enhanced by 2.3 U/ml of rIL-4. A dose-dependent enhancement of IgE-BF was observed in SAC-prestimulated lymphocyte cultures in the presence of rIL-2 as well as rIL-4. These results demonstrate that the mitogen used for lymphocyte activation, T-cell-derived lymphokines such as IL-2 and IL-4, and IgE-specific binding factors (soluble CD23), are responsible for the induction of human IgE antibody production in vitro.