In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory distress syndrome (ARDS) are usually attributed to the release of active enzymes and vasoactive substances from the pancreas. Thoracic duct drainage has been proposed as a means of removing the portion of these substances that drain through retroperitoneal lymphatics before they reach the systemic circulation. This technique was used in six patients with ARDS complicating SAP. The levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at the end of the drainage (Day 8). High plasma concentrations of these products were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase, and trypsin, while similar levels in plasma and lymph were recorded for the other substances. Plasma levels of pancreatic enzymes were weakly correlated with the lung injury score and lymph level of cytokines. These results suggest that in patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could contribute to the development of the lung injury, and that lymphatics are potential vectors of these mediators.