The exchange area of the submandibular salivary gland microvasculature has been measured to allow the value of microvascular permeability (P) to hydrophilic solutes to be calculated from previous measurements of permeability-surface area (PS) products. Glands whose ducts had been ligated for 2 weeks and the contralateral control glands were perfusion-fixed with a modified Karnovsky's fixative after perfusion with a solution containing cationized ferritin, and examined with transmission electron microscopy. Stereological techniques were used to estimate the surface area of the exchange vessels on random thin sections from four control and four duct-ligated glands. The mean exchange surface area in control glands was 512 cm2 g-1 and 336 cm2 g-1 in duct-ligated glands. The fenestral density was calculated to be 0.57% of the exchange surface in control glands and 0.30% in duct-ligated tissue. Molecules of cationized ferritin appeared bound to the luminal surface of the microvascular endothelium, including the surface of the fenestrae to a depth of about 25 nm in both control and ligated glands. These experiments have shown that the exchange surface area of the fenestrated endothelium of the submandibular salivary gland is comparable to that in cardiac muscle but the permeability (P) to small solutes is about 10 times greater. Following ligation of the salivary gland duct, solute permeability falls and an explanation of this, based on the reduced surface area and the nature of the permeability-flow relationship for small solutes is offered.