The permeability of capillaries in the isolated, vascularly perfused cat ileum was studied with the double-indicator diffusion technique. The molecules studied were raffinose, inulin, and beta-lactoglobulin A. Plasma flow through the tissue was increased by local intra-arterial infusions of isoproterenol (a selective mucosal vasodilator) or adenosine (a dilator of the muscularis vasculature). The permeability-surface area product (PS) for all solutes increased with increasing plasma flow. At the highest plasma flow acquired with isoproterenol, PS values for raffinose, inulin, and beta-lactoglobulin A were approximately 40, 20, and 4 ml.min-1.100 g-1, respectively. These data suggest that capillaries in the mucosa-submucosa of the ileum are at least five to seven times more permeable to raffinose and inulin than has been reported for skeletal muscle capillaries. Selective vasodilation of the muscularis region with adenosine reduced PS values for raffinose and inulin at each flow rate studied. The data are consistent with equivalent pore radii of approximately 60 A for capillaries in the mucosa-submucosa and 40 A in the muscularis of the small intestine.