In vitro exposure of isolated rat kidney mitochondria to cyclosporin A, a new immunosuppressive agent with serious nephrotoxic side-effects, leads to alterations of both succinate- and glutamate plus malate-supported respiration in a dose-related manner. ADP- and 2,4-dinitrophenol-stimulated respiration, respiratory control indices, and ADP/O ratios are decreased. The mitochondrial alterations are discussed as possible pathogenetic reasons of cyclosporin A nephrotoxicity.