The studies on human IgE synthesis here summarized provide further insight into the cellular and molecular mechanisms involved in IgE regulation, as well as in the alterations responsible for IgE disregulation in some pathological conditions. They have clearly demonstrated that IL-4 is the essential factor for the induction of human IgE synthesis, since no substantial IgE production in vitro could be obtained in the absence of this lymphokine. Another T cell-derived lymphokine, IFN gamma, negatively regulates the IgE synthesis induced by IL-4. These two lymphokines can be produced by different T helper cells, as shown in mice, but they can also be the product of the same T cell clones. In such a case, the possibility that a given clone provides helper function for IgE seems to be dependent on the balance between the amounts of the two lymphokines produced. The IgE helper activity of rIL-4 appeared to be dependent on the presence in culture of appropriate concentrations of T lymphocytes, suggesting that T-B cell contact or other interleukins, such as IL-2 and IL-6, are needed in IL-4-dependent IgE synthesis. Finally, alterations of one or more of these regulatory mechanisms may play a crucial role in the pathogenesis of diseases characterized by a hyperproduction of IgE.