The physiologic mediators of blood flow to the esophagus are poorly understood. We have investigated the effects of prostaglandins on esophageal blood flow as they are known to alter blood flow in other organs of the gastrointestinal tract. Esophageal mucosal and muscularis blood flow (Q) were measured in New Zealand white rabbits treated intravenously with the prostaglandin analogs misoprostol (PGE1), 16,16-dmPGE2 (PGE2), and iloprost (PGI2, prostacyclin). Esophageal blood flow was measured three times in each rabbit using the radiolabeled microsphere technique after a 30-min continuous infusion of (1) saline (baseline), (2) a low dose, and (3) a high dose of each agent. Iloprost significantly increased esophageal mucosal (fourfold) and muscularis (twofold) blood flow. The other two PG analogs, misoprostol and 16,16-dmPGE2, had no significant effect on esophageal blood flow. Iloprost also significantly increased blood flow to the other organs of the gastrointestinal tract; however, the response was not as dramatic as in the esophageal mucosa. Prostacyclin may have a physiologic role in blood flow regulation to the esophagus and may be involved in pathophysiologic processes in the esophagus, such as increasing mucosal blood flow in response to injury.