A solid-phase-coupled anti-CD3 T cell activation system was used to study the regulation of human IgE production in vitro. Using 5000 peripheral blood lymphocytes from healthy donors, containing 10%-20% B lymphocytes and no monocytes. IgE was produced very efficiently on a per cell basis. A key observation was that apart from interleukin (IL) 4, human transferrin was essential for IgE production. Furthermore it was found that IgE was produced at low densities only; at higher cell concentrations IgE production was completely abrogated, whereas IgM production increased with increasing cell density. This inhibition at higher cell densities is probably mediated by IL2. Addition of low amounts (6 U/ml) of IL2 strongly enhanced IgE and IgM production at low cell densities, but higher concentrations of IL2 (50 U/ml) were strongly inhibitory for IgE production.