Encapsulating peritoneal sclerosis (EPS) is one of the most serious complications of long-term peritoneal dialysis (PD). Long-term PD therapy has been suggested as a risk factor for EPS development among patients in Japan and Australia. Although the primary mechanism of EPS development has not been clarified, histologic changes of the peritoneum associated with prolonged PD are postulated to be causally related. The present article proposes a working hypothesis--the plasma leak-to-response hypothesis--that vascular alterations in the peritoneum of long-term PD patients play a crucial role in the initiation and development of EPS.