In summary, rapamycin offers a unique mechanism of action in immunosuppression, with documented efficacy in terms of reducing the frequency of acute rejection episodes. Clinical trials to date indicate that hyperlipidemia may be a troublesome adverse effect of the agent, with levels of LDLs and triglycerides elevated by 30% to 40% in many treated patients. Cytopenias are also relatively common. In combination with CsA, rapamycin may exacerbate hypertension and nephrotoxicity. Like CsA, FK 506 is also nephrotoxic and may worsen hypertension. However, it may provide greater immunosuppressive efficacy, particularly at lower doses, and clearly exerts less adverse impact on lipid profiles. Its cosmetic advantages may prove especially beneficial in select populations. Limiting factors include glucose intoleance in addition to the usual side effects associated with calcineurin inhibitors. Better definition of the optimal maintenance dose of DK 506 for long-term immunosuppression would facilitate its use. The opportunity to use rapamycin and FK 506 in combination with other newer agents (notably MMF and the humanized monoclonal antibodies) offers great promise that the goal of effective immunosuppression with minimal toxicity for transplant recipients may finally become reality.