Apolipoprotein C-III (ApoC-III) plays an important role in the metabolism of triglyceride-rich lipoproteins and is known to be elevated in patients with uremia. To investigate the role of apoC-III in uremic dyslipidemia, we examined apoC-III, triglyceride levels and lipoprotein particles containing both apoB and apoC-III (LP-Bc) in 27 uremic patients prior to dialysis (predialysis), 30 patients on hemodialysis (HD) and 31 patients on peritoneal dialysis (PD). All three groups of patients had elevated levels of plasma apoC-III (20+/-7 mg/dl for predialysis, 18+/-5 for HD and 22+/-8 for PD, compared to 11+/-3 mg/dl for control subjects [p<0/01 for all comparisons]). ApoC-III was positively correlated with plasma triglycerides in PD patients (r = 0.86, p<0.0001), HD patients (r = 0.67, p<0.0001) and predialysis patients (r = 0.60, p<0.001) as well as in all patients combined (r = 0.75, p<0.0001). ApoC-III was also positively correlated with levels of LP-Bc in all three groups of patients, although this correlation was less strong (r = 0.46, p<0.0001 for all patients combined). In predialysis and PD patients, the majority of apoC-III was found in heparin precipitable lipoproteins, whereas the majority of apoC-III in HD patients was found in HDL, indicating less efficient lipolysis in predialysis and PD patients in comparison with HD. These data support the hypothesis that the elevation of apoC-III in uremia can alter the metabolism of triglyceride-rich lipoproteins, leading to an elevation in triglycerides and LP-Bc. Understanding the mechanism(s) of elevated apoC-III in uremia may help to clarify the causes of uremic dyslipidemia.