SUMMARY1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (M-A) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RToEAC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0-1 M) of sucrose (RTAC; oC = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose.2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mm increase in sucrose concentration, the secretion rate was inhibited by 7v1 %.It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3-4 atm.3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-' are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases.4. ovA for a number of compounds has been measured: urea 0-17; ethanediol 0-27; thiourea 0-51; glycerol 0*69; creatinine 0-81; erythritol 0-91; arabinose 0-96; xylose 0 98; sorbitol 0-98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of 0.A. For molecules with GJA lying between 0-81 and 1 0 an osmotic load of 0-1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with 0-A lying between 0 and 0-81 the concentration of sodium plus potassium was proportional to 0.A. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde.7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.