AGEs (advanced glycation end products) accumulate markedly in the plasma of human subjects with renal failure. We investigated the efficiency of removal of AGEs from the circulation by PD (peritoneal dialysis) and HD (haemodialysis) therapy. Free AGEs were measured by LC-MS/MS in blood plasma before dialysis, in dialysis fluid effusate after a 2-12 h dwell time in the peritoneal cavity of PD subjects, and in the HD dialysate before and after HD therapy. In clinical uraemia, the concentrations of free AGEs in blood plasma were increased up to 50-fold. For example, levels of MG-H1 (methylglyoxal-derived hydroimidazolone) were: normal controls, 110+/-46 nM; PD subjects, 1876+/-676 ( P <0.01); HD subjects, 5496+/-1138 nM ( P <0.001). In PD subjects, the AGE concentration in the effusate increased with increasing dwell time, reaching a maximum at a concentration higher than that in plasma for some AGEs at 4-12 h. This may reflect AGE formation in the peritoneal cavity. In HD, AGE concentrations in HD fluid were decreased markedly from the start to the end of a dialysis session, except that levels of the methylglyoxal-derived AGEs N (epsilon)-(1-carboxyethyl)lysine and MG-H1, and of pentosidine, remained 5-fold higher than control levels. Inadequate clearance of free AGEs may be linked to the increased risk of cardiovascular disease in patients with renal failure.