Vascular changes in the peritoneum were histochemically assessed in patients on continuous ambulatory peritoneal dialysis (CAPD) with ultrafiltration failure. Light microscopy showed extensive interstitial fibrosis, mesothelial denudation and vascular changes. Morphological changes in the vasculature were observed at different levels. The specific changes in the vasculature in these patients were characterized by severe fibrosis and hyalinization of the media of venules. Immunofluorescence microscopy revealed extensive deposition of such extracellular matrices as type IV collagen and laminin in the vascular wall. Electron microscopy revealed a significant increase in collagenous fibers and degeneration of smooth muscle cells in the media. However, the endothelial cells at the levels of vasculature affected were relatively well preserved. These pathological alterations in the vasculature in CAPD patients with ultrafiltration failure suggest that certain toxic factors, such as a high osmolar dialysate or low pH of dialysate, had affected the peritoneal vasculature from the adventitial side rather than the endothelial side. These vascular changes in the peritoneum are thought to be irreversible, associated with deterioration of peritoneal function, and to cause ultrafiltration failure in the patients on long-term CAPD therapy.