During long-term exposure to continuous ambulatory peritoneal dialysis (PD), the characteristics of the peritoneal membrane may be altered. The substrate for nitric oxide synthesis is L-arginine, which may enter cells via the y+ and y+L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway. Maximal capacity for L-arginine transport is higher in patients with a lower dialysis adequacy index. Our aim was to evaluate erythrocyte L-arginine uptake in PD patients at the start and end of a 3-year interval. Our longitudinal study evaluated 8 stable patients on PD who were not using NO donors and who had been free of peritonitis for at least 1 month. Uptake of L-arginine was measured in 2003 and again in 2006. Maximal transport capacity (Vmax, in micromoles per liter-cells per hour) and half-saturation constant (km, in micromoles per liter) were measured in erythrocytes using 14C as a marker and N-ethylmaleimide as inhibitor of the y+ system. For the years 2003 and 2006 respectively, mean +/- standard deviation for total L-arginine uptake Vmax was 749 +/- 182 micromol/L-cells/h and 1146 +/- 365 micromol/L-cells/h (p = 0.016, paired t-test),for y+L Vmax was 180 +/- 58 micromol/L-cells/h and 515 +/- 142 micromol/L-cells/h (p = 0. 002), and for y+ Vmax was 556 +/- 177 micromol/L-cells/h and 662 +/- 267 micromol/ L-cells/h (nonsignificant). The total y+L and y+km were not significantly different. The L-arginine maximal uptake capacity in erythrocytes increased after 3 years of PD treatment. These findings agree with the suggestion of an association between y+L activity and dialysis adequacy or uremia toxicity. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-NO pathway.