Intestinal ++exsorption of salicylic acid, thiopentone, theophylline, and quinidine was measured during perfusion of the intestinal lumen with Tyrode solution. The effect of pectin or bovine serum albumin added to the perfusate on intestinal clearance (CLi) was investigated. Increasing pectin concentration from 0.0 to 0.5, 1.0 and 1.5% gave CLi values for quinidine of 499 +/- 18, 363 +/- 35, 237 +/- 56, and 300 +/- 28 mL h-1 kg-1, respectively. One per cent of pectin in the perfusate also decreased the CLi of thiopentone, but had no effect on the CLi of salicylic acid or theophylline. Pectin may have increased the thickness of the unstirred water layer on the mucous membrane and the resistance of drug exsorption for some drugs. When bovine serum albumin was added, drug binding in the perfusate increased, and the CLi of salicylic acid, thiopentone, and theophylline increased; the CLi of quinidine was unaltered. Co-administration of theophylline with quinidine decreased the CLi of quinidine without affecting quinidine binding in serum or in the perfusate. The CLi theophylline was not affected by quinidine. These observations are consistent with the hypothesis that the exsorption of quinidine is rate-limited by diffusion through the unstirred water layer on the mucous membrane. The CLi of quinidine is affected by the microclimate-pH in the unstirred water layer. An alternative possibility is that quinidine exsorption is mediated by a carrier-transport pathway.