FK506, a new macrolide immunosuppressant agent, is approximately 100 times more potent than cyclosporine. Early clinical trials demonstrated FK506 to be effective in reversing refractory rejection in liver, kidney, and heart transplantation. Like cyclosporine, FK506 has significant nephrotoxicity. The clinical presentation and morphology of FK506 nephrotoxicity are identical to those of cyclosporine. Many animal and in vitro studies suggest that FK506 may be less nephrotoxic than cyclosporine. Studies in humans after transplantation have not confirmed this advantage. FK506 has pursued the same pattern in drug development as cyclosporine, with progressive dose reductions over the years. Studies from this early developmental period suggest that the nephrotoxicity of FK506 and cyclosporine in clinical use are approximately equivalent. Further refinement in the clinical use of FK506 will likely reduce its toxicity further. Appropriate studies conducted at that stage will determine which drug possesses less nephrotoxicity.