Heterotopic homotransplantation of rat hearts was performed and ISS and NK activity levels were determined before and after rejection. The effects of prostaglandin (PGE(2)), cyclosporin A, and indomethacin on the acceptance of transplanted hearts as well as on ISS and NK activity were studied. PGE(2) and PGI(2) significantly extended survival when compared to a control group, while indomethacin decreased survival. ISS peaked 4 days before the rejection of transplanted hearts, suggesting its usefulness as a marker of rejection. Moreover, NK activity was significantly higher around the time of rejection, suggesting the importance of NK cells in this process. Finally, rejection was suppressed by administration of PGE(2).