This study examined the morphologic features of the parietal peritoneal membranes of 130 patients undergoing peritoneal dialysis (PD) and compared them with the features of the peritoneal membranes of normal individuals, uremic predialysis patients, and patients undergoing hemodialysis. The median thickness of the submesothelial compact collagenous zone was 50 microm for normal subjects, 140 microm for uremic patients, 150 microm for patients undergoing hemodialysis, and 270 microm for patients undergoing PD (P < 0.001 for all versus normal subjects). Compact zone thickness increased significantly with the duration of PD therapy [0 to 24 mo, 180 microm (n = 58); 25 to 48 mo, 240 microm (n = 24); 49 to 72 mo, 300 microm (n = 13); 73 to 96 mo, 750 microm (n = 16); >97 mo, 700 microm (n = 19)]. Vascular changes included progressive subendothelial hyalinization, with luminal narrowing or obliteration. These changes were absent in samples from normal subjects but were present in 28% of samples from uremic patients and 56% of biopsies from patients undergoing PD. In the PD group, the prevalence of vasculopathy increased significantly with therapy duration (P = 0.0001). The density of blood vessels per unit length of peritoneum was significantly higher for patients with membrane failure and was correlated with the degree of fibrosis (P = 0.01). For the first time, a comprehensive cross-sectional analysis of the morphologic changes in the peritoneal membranes of patients undergoing PD is provided. The infrequency of fibrosis in the absence of vasculopathy suggests that vasculopathy may predispose patients to the development of fibrosis. This study provides a sufficiently large cohort of samples to allow structure-function relationships to be established, as well as providing a repository of tissue for further studies.