The redundant and pleiotropic effects of cytokines in transplant models have been shown both in vitro and in vivo. IL-2 is clearly not necessary for allograft rejection, possibly due to upregulated IL-15. We examined IL-15 expression using mixed lymphocyte culture (MLC) as an allorecognition model. IL-2 and IL-15 levels were measured by enzyme-linked immunoassay after 120 hours of culture. Cell proliferation in MLC was examined using [(3)H]thymidine uptake in the presence of either anti-IL-2Ralpha chain antibody or anti-IL-2Rgamma chain antibody. While IL-2 was detectable in cell supernates of MLC, IL-15 was not. Stimulation with an Anti-IL-2 gamma chain antibody which blocks the IL-2 gamma chain, a common unit in IL-2/IL-15 receptors, failed to produce additive antiproliferative effects after maximum inhibition by anti-IL-2alpha chain antibody, which is specific for IL-2. In conclusion, experiments in the MLC model suggest that allorecognition upregulates IL-2 but not IL-15 expression.