Infiltration of antitumor agents into subcutaneous tissues may either result in a local area of self-resolving inflammation or progress to full-thickness loss of skin and underlying vital structures. Inadvertent extravasation of adriamycin can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be release of oxygen free radicals into the tissue. After adriamycin extravasation, the treatment groups were made up according to drugs used, EGb 761, pentoxifylline, alpha-tocopherol acetate, and alpha-tocopherol succinate in rats. To prevent the necrosis and to decrease the tissue malondialdehyde levels, the most effective agent was found to be EGb 761, and pentoxifylline was also effective (P < 0.001). No difference was found between topical lanoline and saline (P > 0.05). The maximum ulcer diameter was obtained in 2 weeks. The maximum tissue malondialdehyde levels were obtained in 24 h, and in comparison to the control group the treatment groups showed lower levels. Our aim is to show the role of free radicals in the formation of skin necrosis as a cause of adriamycin extravasation and to prevent or decrease the skin necrosis using various free radical scavengers. (C) 1998 Academic Press.