To evaluate the effects of short-term starvation on gastric emptying in normal and obese subjects, the relationship between gastric emptying and oral glucose tolerance, and the mechanisms responsible for the delay in the systemic appearance of oral glucose observed after short-term fasting, we determined the effects of a 4-day fast on 1) gastric emptying and oral glucose tolerance in normal subjects and 2) gastric emptying in obese patients. Gastric emptying of 75 g glucose (320 ml) labeled with 99mTc colloid was measured in 12 healthy volunteers and 11 obese subjects after 12-h and 4-day fasts. In seven other obese subjects, the effect of a 4-day fast on gastric emptying of 320 ml normal saline was quantified. Gastric emptying of glucose was slower after the 4-day than after the overnight fast in both normal (P = 0.02) and obese (P < 0.001) subjects, with no difference between the two groups. In normal subjects, the rate of gastric emptying was related directly to the rise in plasma glucose at 30 min (r = 0.60; P < 0.05) but inversely to the plasma glucose at 180 min (r = -0.64; P < 0.02). In the obese subjects, gastric emptying of saline was not affected by fasting. These observations indicate that 1) gastric emptying of glucose is retarded by a 4-day fast, 2) the changes in gastric emptying reported in obesity may reflect different patterns of prior nutrient intake, and 3) delay in gastric emptying accounts for the slower systemic appearance of glucose after fasting.