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High-affinity interleukin 2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells.To exploit this difference in IL-2R expression, anti-Tac-M, a murine monoclonal antibody specific for the IL-2Ra chain, was used to inhibit organ allograft rejection. However, the use of murine anti-Tac as an immunosuppressive agent was limited by neutralization by human anti-murine antibodies and by weak recruitment of effector functions. To circumvent these difficulties, a humanized antibody to the IL-2R, anti-Tac-H, was prepared. This molecule is human with the exception of the hypervariable segments, which are retained from the mouse. In vivo survival of anti-Tac-H is 2.5-fold longer than simultaneously administered anti-Tac-M (terminal t y2, 103 hr vs. 38 hr).