In vivo-activated, committed donor-specific cytotoxic lymphocytes (cCTL) can be propagated and expanded from endomyocardial biopsies (EMB) in IL-2-enriched medium especially during an acute rejection episode. We report here our efforts to detect these cCTL by the same technique in peripheral blood at the moment of rejection and when no rejection was diagnosed. During or just before rejection, significantly less frequent (P less than 0.01) donor reactive cCTL were found in PBL samples (two out of 20) than in the simultaneously taken EMB samples (13 out of 19). Donor B-LCL and/or third-party B-LCL were lysed by 15 PBL samples. Inhibition studies revealed that this lysis was due to LAK-like cytotoxicity. The results show that peripheral blood does not reflect intra-graft events, which is probably the reason for the irreproducible results of diagnosis of rejection by monitoring immunological parameters in the peripheral blood.