The uptake of L-lysine was examined in isolated renal cortical tubules. Lysine was actively taken up by the renal tubule cells isolated from 7-week-old rats. No metabolism of the transported lysine was found. There was no evidence for sodium-dependence of lysine uptake. Concentration dependence studies revealed that the lysine was taken up by one saturable transport system with a Km of 1.66 mmol/l and Vmax of 7 mmol/l intracellular fluid per 10 min. Lysine also entered by a non-saturable pathway. Arginine and ornithine inhibited the initial uptake of lysine. Cystine increased the efflux of lysine from preloaded renal cells via hetero-exchange, indicating that a common system exists for these two amino acids.