Hemolytic-uremic syndrome (HUS) is a well-recognized complication of cyclosporine (CyA) therapy. Transplant recipients with this complication are frequently switched to tacrolimus, although this drug has also been implicated. We report a case of a renal transplant recipient who developed severe graft dysfunction due to biopsy-proven HUS after receiving CyA. Renal function and hemolytic parameters improved with discontinuation of the drug, but they deteriorated again after commencement of tacrolimus 15 days later. A second transplant biopsy demonstrated fresh lesions diagnostic of HUS. Hemolytic parameters resolved with discontinuation of tacrolimus. This is the first report of metachronous HUS being caused in a renal transplant by both CyA and tacrolimus. We therefore believe that caution should be exercised when using tacrolimus as rescue therapy in patients with CyA-induced HUS.