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The major immunophilins that bind cyclosporine (cyclophilin) and FK-506/rapamycin (FK-BP 12) have been well characterized. They possess rotamase activity, which is inhibited by the immunosuppressant that binds to them. The immunosuppressive action does not appear to be coupled to rotamase activity. The literature is reviewed on some possible mechanisms of immunosuppression. Minor immunophilins of 14, 36, and 52 kDa have also been isolated and partially characterized. Receptor assays employing immunophilins have been developed.