Till now there is no consensus about appropriate contrast agents for use in clinical inves-tigation in suspected perforation of the esophagus. Gastrografin most widely used water-solu-edema, leading to death occasionally if detection of fistulous tract and can induce pulmonary edema leading to death occasionally if aspirated. Barium sulphate has been contraindicated without actual evaluation of its effect onmediastinum by experimental and clinical study. The purpose of this experimental study is to evaluate the type of tissue reaction and its severity in mediastinum and. as result to propose appropriate contrast agents in various clinical situations of suspected esophageal leakage. Barium sulphate Hytrast Gastrografin Telebrix, Hexabrix Amipaque Niopam and Ultra-vist were injected into mediastinum of 20 rats in each. The tissue reaction of injection sites serial follow-up from 1 day to 8 weeks after injection, The results are as follows. 1. Barium sulphate and Hytrast produced highly significant(p<0.01) tissue reaction compared control group and proved to be safe in the situation of leakage into mediastinum, 3. Injected barium caused no death during 8 week follow-up inspite of large injected amount and histologically produced localized indolent granuloma agter 4 weeks which is expected not to cause any delayed complications. In consideration of above results superior physical characterstics of barium sulphate and drawbacks of Gastrografin we concluded as foll2ows. 1. For postoperative assessement of esophageal anastomosis Barium sulphate is the contrast agent of choice. 2. In supstected gross leakage into mediastinum or esophagopleural fistula water-soluble agents are recommended. In high risk patients of pulmonary aspiration Hexabrix is safer than Gastrografin. 3. If leakage is not demonstrated with water-soluble agents Barium study must be repeated to find missed fistulous tract.