In microperfusion experiments renal tubular reabsorption of 35S- and 14C-labelled L-cysteine (= cys), L-cystine (= cys-cys), and L-cystathionine was measured in vivo et situ at different initial concentrations. The interactions of cys and cys-cys with several neutral amino acids were investigated. The cys reabsorption mechanism was found to be saturable and has a high capacity and a low affinity for cys. An Jmax-value of 3.22 +/- 0.88 nmol X m-1 X s-1 and a Km-value of 7.5 +/- 0.7 mmol X l-1 were estimated. A saturation of cys-cys reabsorption could not be demonstrated. The fractional reabsorption rate (= FRR) of cys-cys was about 85% at initial concentrations of 0.01, 0.08, and 0.4 mmol X l-1 after a perfusion distance of 2 mm. The FRR of L-cystathionine at an initial concentration of 0.115 mmol X l-1 was only 30% under the same conditions. After perfusion of tubule segments between late proximal and early distal loops the recovery of cys, cys-cys, and cystathionine was smaller than 10%. The FRR of cys was decreased only by L-methionine. Six other neutral amino acids had no effect. On the other hand the FRR of cys-cys was reduced significantly by any of the tested neutral amino acids. The inhibitory effect increased in the order L-alanine less than L-methionine less than L-citrulline less than alpha-aminoisobutyric acid less than L-phenylalanine less than cycloleucine. The FRR of L-methionine and L-phenylalanine was slightly reduced in the presence of cys. It is concluded from these results that cys-cys shares a transport system with other neutral amino acids which is not identical with the reabsorption mechanism for cys. Reabsorption of cys, cys-cy, and cystathionine occurs also in a tubular section between late proximal and early distal sites.