In accordance with results obtained in another culture system, it has previously been shown that human B cells frequently switch to immunoglobulin E (IgE) when they are co-cultured with irradiated mutant EL4 thymoma cells (which provide a CD40 ligand-mediated B cell activation signal), T cell supernatant and recombinant interleukin (IL)-4. However, because of the potentially severe side effects of IgE, such as anaphylaxis, B cells could have a limited capacity to produce this isotype. The IgE secretion rate of plasma cells is not known. In the present study, we compared the secretion rates for different Ig classes by means of limiting dilution analysis of plasmocytic cells that were harvested after 8 to 9 days from primary EL4/B cell cultures and titrated into secondary cultures in the presence of a cell proliferation-blocking concentration of hydroxyurea. These cells secreted Ig at constant rates for periods of up to 2 weeks; IgE secretion was IL-4 independent. The mean cellular secretion rates were similarly high for IgE (150 pg/cell/24 h) and other isotypes (IgM 273 pg, IgG 112 pg, IgA 136 pg/cell/24 h). In terms of molecules per min this represents 3.3 x 10(5) for IgE versus 1.2 x 10(5) for IgM, 3.1 x 10(5) for IgG and 3.6 x 10(5) for IgA. The relative frequency of IgE-secreting cells was only 0.3% of the total number of Ig-secreting cells, suggesting a small size of IgE-producing clones in this in vitro system. Whether this is relevant regarding an in vivo response is not known. Clearly, the Ig secretion capacity of plasma cells would not limit an IgE response in the absence of extrinsic control.