We applied cloned human T lymphocytes established in our laboratory to evaluate the mode of action of Cyclosporine (CsA) and FK506. Phenotypic and functional analysis led us to conclude that HTL403 was a helper T cell clone and HTL805 a cytotoxic one. Susceptibility of HTL-403 to the immunosuppressants demonstrated that alloantigen-driven proliferative response can recover to the rIL2-driven level by the addition of rIL2 at higher concentration of the agents. Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. FK506 showed remarkable suppressive effect on the proliferative response of HTL-805 even at a considerably low concentration, while CsA suppressed such a response dose-dependently. We concluded that FK506 can be used to reverse ongoing acute rejection as well as to prevent acute rejection.