Rapamycin (RAPA) is a new immunosuppressive drug with a potency similar to that of FK506 and up to a 100-fold greater than that of cyclosporine (CsA). RAPA has shown to be efficacious in the prolongation of allograft survival in a number of animal models. In early studies, RAPA was administered on a dose/weight basis, with little attention given to its effective blood concentration. Details describing the approaches used to establish a therapeutic range for the drug in animal transplant models are described. Guidelines for therapeutic monitoring of the drug are proposed. It is hoped that such preclinical work in animals will facilitate establishment of monitoring protocols for the drug in clinical trials.