Ultrafiltration failure (UFF) is a common complication of long-term peritoneal dialysis (PD). Functionally UFF is in most cases characterized by an enhanced peritoneal mass transfer area coefficient for glucose (PS(g)) combined with a largely unchanged peritoneal glucose osmotic conductance (L(p)Ssigma(g)). Morphologically, marked UFF occurs with fibrosis of the submesothelial zone in the peritoneum, combined with vasculopathy and vascular proliferation in deeper tissues. To computer simulate UFF, changes both in the vasculature and in the interstitium have to be taken into account. For that purpose, we used a three-pore membrane/fiber matrix serial barrier model, applying the three-pore model to the capillaries and the fiber-matrix model to the interstitium. The parameters of the three-pore model have been published previously. The interstitial fiber density was set at 0.5% (vol/vol) and the fiber radius (r(f)) at 6 A during control. If the interstitial fiber density was increased from 0.5 to 3%, and r(f) to 7.5 A (cf. collagen) while the capillary surface area was increased by 40% from control, then PS(g) increased from 9.3 to 11.5 ml/min, while the UF coefficient (L(p)S) was largely unchanged. Further increases in vascular surface area combined with further increases in fiber density caused further increments in PS(g), whereas L(p)S remained unchanged. It is concluded that a matrix of fibers coupled in series with a three-pore membrane may be used for simulating the pathophysiological alterations occurring in the peritoneum in UFF, explaining the commonly observed "uncoupling" of small solute transport (PS) from the peritoneal UF coefficient (L(p)S) in this condition.