Permeability-surface area products for the fenestrated capillaries in the perfused cat submandibular gland have been measured for graded lipid-insoluble molecules using the single-passage, multiple-tracer dilution technique. 2. The permeability-surface area for [57Co]cyanocobalamin (mol. wt. 1353) increased as the perfusion flow was increased, but reached a constant value of 4.11 +/- 0.25 ml.min-1.g-1 (mean +/- S.E., n = 9) at flows above 8 ml. min-1.g-1. For [125I]insulin (approximate mol. wt. 6000) it was 1.80 +/- 0.13 ml.min-1.g-1 (mean +/- S.E., n = 9) and apparently diffusion-limited at all the high flow rates studied. A similar permeability-surface area product was measured for [14C]inulin (mol. wt. 5500): 1.76 +/- 0.10 (mean +/- S.E., n = 4). 3. Permeability-surface area values for cyanocobalamin and insulin in the salivary gland are respectively about 20 and 200 times larger than the estimates reported for the continuous capillaries of cardiac and skeletal muscle. 4. The permeability-surface area (PS) ratio [57Co]cyanocobalamin/[125I]insulin (2.33 +/- 0.15, mean +/- S.E., n = 9) was significantly greater than the apparent ratio of their free diffusion coefficients (1.76), suggesting restricted diffusion of insulin relative to cyanocobalamin across the capillary endothelium. 5. Permeability-surface area products for the smaller molecular weight tracers (22Na, 86Rb and 51Cr-EDTA (mol. wt. 357)) increased continuously with perfusion rate, indicating flow-limited solute exchange. The PS ratio of Rb/EDTA was close to unity whereas the corresponding free diffusion ratio is 3.85. 6. The high permeability-surface area values measured were thought to be associated with the fenestrae which appeared to act as high concentrations of 'small pores' rather than as 'large pores'.
