The ability to detect rejection of human cardiac allografts depends on endomyocardial biopsy diagnosis. Because cytokines are known to mediate allograft rejection events, we chose to examine serum levels of specific cytokines and receptors (interleukin-2 [IL-2], IL-2 receptor [IL-2R], and tumor necrosis factor alpha [TNF-alpha]) and to correlate those levels with findings on endomyocardial biopsy. Sequential sera samples from 23 cardiac allograft recipients were examined for the cytokine levels mentioned, and data correlated with findings on endomyocardial biopsy. Briefly, no statistically correlation of serum cytokine or receptor levels with the stage of allograft rejection was found. When sequential serum cytokine levels were determined in patients experiencing humoral and cellular allograft rejection events, the levels of TNF-alpha appeared to correlate well with endomyocardial biopsy findings. IL-2 and IL-2R levels in two patients who never experienced rejection were elevated on occasion, but TNF-alpha levels were always negative. In summary, measurement of serum cytokine (IL-2, IL-2R) levels in cardiac allograft recipients does not appear to correlate with findings on endomyocardial biopsy; however, elevated levels of TNF-alpha appear to predict more severe humoral allograft rejection episodes and may be helpful in this regard.