Clones of human B lymphocytes, obtained after immortalization with Epstein-Barr virus (EBV) of single CD19+ B cells and expansion in the absence of human T lymphocytes, produced mRNA for the T cell cytokines interleukin(IL)-2, IL-4, and interferon (IFN)-gamma. As detected by reverse transcriptase-polymerase chain reaction, IL-2 mRNA was expressed only after stimulation with the combination of phorbol 12-myristate 13-acetate (PMA) plus ionomycin. IL-4 mRNA was constitutively detectable in all (10/10) EBV-transformed B cell clones, and the mRNA for IFN-gamma was constitutively present in half of the clones. In contrast to IL-2 mRNA, the expression of IL-4 and IFN-gamma mRNA could be increased by PMA alone. Most of the clones produced IL-2 bioactivity and immunoreactive protein, but neither IL-4 nor IFN-gamma protein secretion was detected. The intriguing question raised by these results is whether IL-2 secretion could contribute to the immune control of EBV-infected B lymphocytes by cytolytic T cells, and whether normal B lymphocytes can potentially be induced to express certain cytokines including IL-4 in response to the appropriate activation signals.