The responses of the human proximal stomach to distension were studied in 22 healthy volunteers using an intragastric polyethylene bag, inflated progressively in 30-ml steps until the limit of tolerated volume was reached. Three successive inflations were carried out during the fasting state followed by a fourth inflation after ingestion of 250 ml of either a nutrient meal or isosmolar saline. The first inflation showed an initial nonlinear pressure rise (slope of logged pressure vs. volume = 114.6 +/- 10.0 log mmHg/ml x 10(-5)), which was then followed by the development of a plateau phase, in which further distension did not increase intragastric pressure. The slopes of the subsequent fasting inflations were significantly lower than that of the first inflation (P < 0.01) but were similar to each other (slope 83.0 +/- 5.4 and 79.8 +/- 5.7 log mmHg/ml x 10(-5)), indicating that distension-induced gastric relaxation had occurred. After saline ingestion, responses to distension were similar to those during the fasted state. After the nutrient meal ingestion, however, the slope decreased to 60.3 +/- 7.7 log mmHg/ml x 10(-5) (P < 0.01 vs. saline), indicating nutrient-induced gastric relaxation. Our study demonstrates that the pressure-volume characteristics of the proximal stomach are modulated both by distension and by the presence of nutrients in the upper gut, which appear to operate independently.