The reverse transcriptase polymerase chain reaction (RT-PCR) technique was used to analyse cytokine gene expression in relation to acute cardiac rejection. Expression of interleukins, IL-2, IL-4, IL-6 and IL-10 mRNA was studied in sequential endomyocardial biopsies (EMB) and in graft-infiltrating lymphocyte (GIL) cultures propagated from EMB taken after heart transplantation. The cytokine gene expression of GIL propagated from EMB taken during an episode of rejection and of immunological quiescence was comparable. In contrast, posttransplant EMB showed selective IL-2 gene expression when rejection was diagnosed. IL-4 mRNA was absent in pretransplant EMB but present in posttransplant EMB taken during periods of rejection and of immunological quiescence. Both IL-6 and IL-10 transcripts were found in pre- and posttransplant EMB. These findings confirmed that IL-2 is specifically involved in cardiac rejection, while IL-4 may play a role in immune responses leading to graft rejection or graft tolerance.