Gastric emptying of dietary fat is affected by both chemical and physical factors; but when ingested as a free oil or an aqueous emulsion, fat may empty most rapidly immediately after the meal. In contrast, gastric transit of 1- to 3-mm spheres (like those of enterically coated pancreatins) is known to vary inversely with sphere diameter; and spheres leave the stomach initially slowly, if their diameter is > or = 1.6 mm. Our objective was to determine whether 2-mm microspheres of Pancrease would empty much more slowly than free or emulsified oil and whether 1.2-mm microspheres of Creon would empty as fast as free oil. We used a gamma camera to track the concurrent gastric emptying of 123I-labeled oil and 113mIn-labeled spheres of Pancrease or Creon in pancreatic-insufficient subjects with cystic fibrosis who ingested 20 g of free oil in spaghetti meals or 20 g of oil emulsified in a milk meal. We found that either type of oil emptied rapidly initially but slowed later, whereas either dosage form emptied slowly initially but rapidly later. Unexpectedly, the smaller spheres of Creon emptied about the same as Pancrease did after the spaghetti meal. For example, 50% of oil but < 25% of either dosage form had left the stomach by 90 min after the meals. Both dosage forms were lipophilic, forming aggregates in vitro. We concluded that the gastric emptying of either dosage form frequently lagged behind the emptying of oil from ordinary meals. We speculated that the similar transits of the 1.2-mm Creon and the 2-mm Pancrease resulted from aggregation of these microspheres in the presence of free oil.