The characteristics of cyclosporin A transport have been studied in cultured kidney epithelial cell line LLC-PK1. The uptake of cyclosporin A by LLC-PK1 cells was time-dependent and reached a steady state at about 30 min. The initial uptake was saturable and was inhibited by cyclosporin A analogs, cyclosporin C and D and by verapamil, but not by metabolic inhibitors such as 2,4-dinitrophenol and rotenone. Cyclosporin A uptake as well as efflux was strongly dependent on temperature. The Arrhenius plot for cyclosporin A uptake was biphasic, whereas the Arrhenius plot for sulfanilamide uptake, which is transported by a simple diffusion, was linear. These results indicate that a specific mechanism is concerned in the transport of cyclosporin A in LLC-PK1, cells.