The understanding of the regulation of cytokine production and T-cell proliferation by other cytokines is far from complete. We have examined the supernatant concentration of different cytokines in cultured peripheral blood lymphocytes (PBL) incubated with monoclonal antibodies against the interleukin-2 receptor (IL-2R) or interleukin-4 receptor (IL-4R) complex in order to analyse the importance of these receptors in the production of other cytokines. The PBL cultures were stimulated with phytohaemagglutinin and phorbol myristate acetate. The addition of anti-Tac to PBL cultures resulted in increased free IL-2 due to blockade of IL-2R. MR6 (a monoclonal antibody against IL-4R) did not affect the supernatant concentration of IL-2 in cultured PBL. Blockade of IL-2R or IL-4R both resulted in increased IL-4 in supernatant. The increase in supernatant concentration of IL-4 in PBL cultured with MR6 was due to a direct interaction with the IL-4R complex but the increase in IL-4 with anti-Tac was due to the accumulation of free IL-4 as an effective blockade of IL-2R prevented the full expression of IL-4R. Neither anti-Tac nor MR6 affected the IL-6 production by activated PBL, suggesting the existence of an IL-2- and IL-4-independent pathway. Blockade of IL-2R or IL-4R both resulted in a reduction of interferon-gamma (IFN-gamma) production, indicating that both endogenously generated IL-2 and IL-4 are important mediators of IFN-gamma induction in PBL cultures stimulated with T-cell mitogens.