Wound debridement for the removal of necrotic tissue is a crucial step in wound management. Enzymatic wound debridement is one example of a method currently used that removes necrotic tissue with proteases and offers selectivity without affecting healthy adjacent tissue. Proteolytic enzymes for wound debndement are commercially available as ointments. The authors previously proposed and demon- strated feasibility on small lab animals-an alternative mode of deliv- ery of proteolytic enzymes for wound debridement with continuous streaming of protease solutions. The present study describes the impact of streaming of papain solut ions, fort ified by the incorporation of hypertonic agents, onto an experimental larger chronic wound model in pigs. Debridement of approximately half of the necrotic tis- sue mass was achieved within 6 to 11 h of streaming of papain solu- tions onto these experimental wounds. No adverse effects or notice- able morphological changes to the wound surface or its immediate surroundings were noted, indicating enzyme selectivity and preference for attacking necrotic tissue. The mechanism of enzymatic attack on the necrotic tissue is also discussed. In the control group, streaming of the basic solution formula (devoid of papain) was performed-no debridement of necrotic tissue was noticed in this case. The results indicate that the streaming delivery mode for enzymatic debridement is a highly effective tool designed to be completed in a few sessions. thus paving the way for extension of its application in clinical trials on humans.