Background: Volume overload is thought to be the most important cause of hypertension in peritoneal dialysis (PD) patients. However, there is also evidence that normalization of volume overload is not always accompanied by a drop in blood pressure (BP). In the present study, we hypothesized that dysregulation of peripheral resistance due to endothelial dysfunction would constitute an important determinant of BP response in overhydrated PD patients. Methods: We performed an observational, prospective cohort study including all prevalent PD patients at the Peking University Third Hospital between 1 June 2006 and 30 November 2006. After baseline measurements, including echocardiography and bioelectrical impedance analysis, patients fulfilling inclusion criteria were reevaluated after 2 months of follow-up. All patients that exhibited significant changes in BP and extracellular water (ECW) between 2 visits were asked to undergo a second ultrasound. These patients were then divided into group A (parallel change between BP and ECW; n = 12) and group B (paradoxical change between BP and ECW; n = 10). Results: The cohort included 22 patients (13 males) with a mean age of 59 +/- 13 years, on dialysis for 23.3 +/- 32.6 months. There were no baseline differences between groups A and B. However, while patients in group A significantly increased their cardiac output, total peripheral resistance remained stable. In group B, cardiac output did not change significantly but total peripheral resistance decreased significantly. Conclusion: In PD patients, a significant increase in fluid volume is not necessarily linked to a significant increase in BP. Rather, the change in total peripheral resistance was found to be the most important determinant of the extent to which increased fluid volume affected BP.