The activities of five serum enzymes in beagles with high-velocity gunshot extremity wounds have been followed for six days after wounding. Creatine phosphokinase (CPK) reflect the greatest sensitivity to muscle damage. Lactic dehydrogenase (LDH) and alkaline phosphatase showed minimal increases. Debridement of wounds netted a return to normal enzyme values a day earlier than in wounds not treated. Complete debridement resulted in enzyme increases 35% to 75% less than the elevations observed in the nondebrided group. Otherwise, no difference could be recorded between the effects of partial or complete debridement upon the enzyme changes. The source of CPK, LDH, glutamic oxaloacetic transaminase, and aldolase in the serum is the nonviable resected muscle as well as surrounding injured muscle. Secondary elevations of the activity of these enzymes are considered due to damage to other organs or secondary damage to skeletal muscle.