Cyclosporine (CyA) is a potent immunosuppressant, but possesses toxicities which prohibit its unrestricted dosing in patients. The topical administration of CyA could serve to localize the immunosuppressive effect, or could serve as an administration route for patients who cannot tolerate the oral route of administration. We evaluated the potential for transdermal delivery of cyclosporine in rabbits. We sensitized six rabbits to dinitrochlorobenzene (DNCB), treated them topically with either 100 mg CyA or the vehicle, and repeated the DNCB skin testing at 15 and 28 days at the site of administration and at a distal site. In the CyA treated rabbits, significant increases in the suppression of the reaction to DNCB were observed from the control to the 15 day test, and from the 15 to the 28 day testing. Significant differences were also observed between reaction to DNCB at the site of CyA administration and at the distal site. While blood concentrations demonstrated slow and variable absorption of the topically administered CyA, concentrations greater than 1000 ng/ml were frequently observed in blood. We conclude that the local versus a systemic dermatologic effect of CyA can be achieved, and that high blood concentrations are present after topical CyA administration in this model.