The location of the site involved in the secretory response of rat jejunum and colon to ACh was investigated by selectively damaging either the villi of the jejunum and the surface epithelium of the colon or the crypts. 2. The secretory response induced by ACh was measured both in terms of changes in electrical activity and chloride fluxes. 3. Exposure of the mucosa to 2 M-Na2SO4 for 30 min selectively damaged the jejunal villi and colonic surface epithelium but did not reduce the increased potential difference and current generated by ACh. 4. When resistance changes were taken into account the colonic response was markedly increased after Na2SO4 treatment although the jejunal response was unchanged. Under control conditions ACh reduced net Na absorption and stimulated Cl secretion by the colon. After exposure to Na2SO4 only the Cl secretory component of the ACh response remained, thus accounting for the enhanced effect. 5. Cycloheximide, administered I.V. at a dose of 12 mg/kg, damaged the crypts after 2 hr without affecting the villi of the jejunum or the surface epithelium of the colon. After cycloheximide treatment the increased potential difference, current and net Cl secretion induced by ACh were significantly reduced. 6. The crypts therefore appear to be the site primarily involved in the secretory response of rat jejunum and colon to ACh, although in the colon an inhibitory effect on the Na transport process located in the surface epithelium was observed.
