Chronic diarrhea may occur when gastrointestinal transit is abnormally rapid. We hypothesized that oleic acid given prior to a meal would slow gastrointestinal transit and reduce diarrhea by activating nutrient-triggered inhibitory feedback mechanisms in the small intestine. Transit time was measured in eight normal subjects following ingestion of a control emulsion (0 ml oleic acid), and in 45 patients with chronic diarrhea following ingestion of emulsions containing 0, 1.6, and 3.2 ml oleic acid. Stool volume and frequency on and off treatment were compared. Transit time in normal subjects was 102.4 +/- 11.2 min (mean +/- SE). Transit times in patients was shorter at 29.3 +/- 2.8 min with the 0-ml dose (P < 0.001), but increased to 57.2 +/- 4.5 min with the 1.6-ml dose and to 83.3 +/- 5.2 min with the 3.2-ml dose (P < 0.001). In the 18 patients who provided stool records, frequency of bowel movements decreased from 6.9 +/- 0.8 to 5.4 +/- 0.9 bowel movements/24 hr (P < 0.05) and stool volume decreased from 1829.0 +/- 368.6 to 1322.5 +/- 256.9 ml/24 hr with treatment (P < 0.05). An emulsion containing oleic acid slowed gastrointestinal transit and reduced diarrhea by activating nutrient-triggered inhibitory feedback mechanisms in the small intestine.