A study was carried out to elucidate the physiological mechanisms responsible for the intestinal secretion produced by venous pressure elevation. In dogs, measurements were made of the rate and composition of small intestinal secretion, rate of flow and composition of intestinal lymph, plasma composition, and mucosal water content, all in response to elevations of intestinal venous pressure. Venous pressure elevations above a threshold value of 30-35 cm H2O produce secretion at a rate of approximately proportional to the value of the pressure minus the threshold value. Above the threshold value, there were large increases in the rates of lymph flow and net sustained transcapillary filtration. These rates were also roughly proportional to the incremental venous pressure. It is concluded that intestinal secretion produced by elevated venous pressure is almost surely secretory filtration, a passive process with the driving force for secretion an increase in mucosal tissue fluid pressures to values of only some 4-6 cm H2O. The increased tissue fluid pressure not only provides the driving force but also produces an increase in the hydraulic permeability of the epithelium without which the driving force would be ineffective. The transepithelial channels are large enough to permit insulin to pass freely and even plasma protein to pass in large amounts, and hence are most probably intercellular. Secretory filtration probably represents a general pathophysiological response of transporting epithelia to elevated tissue fluid pressure. It is proposed that the threshold value for secretion and associated changes is explained by dilution of the tissue fluid protein colloid osmotic pressure in a small subepithelial, juxtacapillary compartment.