Human peripheral blood cells produce immunoglobulin-binding factors upon stimulation with purified protein derivative. The binding factors from 2 healthy individuals were purified by IgE affinity chromatography. IgE-suppressive activity was demonstrable using the IgE-producing human myeloma cell line U-266 as an assay system. The effect of the suppressive factor seems to be reversible, isotype specific, as the immunoglobulin synthesis in the IgGk-producing U-1958 myeloma line was not affected, and selective for the epsilon heavy chain. The results also suggest that this suppression is not the result of a decrease in DNA synthesis or suppression of protein synthesis in general.