Oral administration of Gardrin (enprostil), a synthetic prostaglandin E2 structural analogue, is associated with a rapid reduction in serum lipoproteins as well as a reduction in meal-stimulated increments for glucose, insulin, and glucose-dependent insulinotropic peptide (GIP). The latter effects appear to be related to be a reduction in carbohydrate absorption. To test the effects of enprostil on an oral fat challenge, 6 healthy males received in random order 35 micrograms enprostil (enp) and placebo (pla), each as a single dose. Thirty minutes following study drug, subjects consumed an 856 kcal test meal with 76 g total fat (80%), 29 g carbohydrate (14%), and 14 g protein (6%). Compared with placebo, enprostil resulted in significant or near significant reductions in insulin, total triglycerides (TG), chylomicron TGs, and GIP while glucose was modestly elevated. The integrated areas under the insulin, GIP, TG, and chylomicron curves were reduced by 59% for insulin and greater than 90% for the remainder, respectively. Thus a single dose of enprostil appears to decrease alimentary lipemia through an effect on chylomicron formation and/or clearance. Other effects, such as a delay in gastric emptying, may be contributory. These observations may have potential therapeutic applications, and additional studies are ongoing to define mechanisms.