It has been observed previously that a hematoma affects skin flap survival adversely through free radical action. The current study was undertaken to determine whether similar mechanisms are operative in skin grafts. The experiment was divided into two parts. During part I, 2 x 2 cm2 split-thickness skin grafts (STSGs) were harvested from 18 Fischer rats and were divided randomly into three groups (each consisted of six grafts), and incubated with plasma, blood, and blood plus 70 mg deferoxamine for 48 hours respectively. Tissue samples were assayed for lipoperoxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and nitric oxide synthase (NOS). During part II, 36 STSGs were harvested and were divided randomly into three groups. The grafts were incubated as in part I for 48 hours. The STSGs were then affixed to the same dimension recipient beds created on the back of 36 inbred rats. Survival was evaluated 7 days postoperatively. The results showed that there was no significant difference in MDA and NOS levels between each incubated graft group in part I. Only the SOD level in both grafts incubated with plasma and blood plus deferoxamine were significantly higher than the grafts over blood alone (p < 0.05). During part II, there was no significant difference of the average STSG survival percentage between the groups incubated with blood and blood plus deferoxamine (35.8 +/- 6.5% and 52.0 +/- 9.5%). The survival percentage of the group incubated with plasma was 81.8 +/- 7.3%, which was significantly higher than the other two groups (p < 0.01). The authors concluded that unlike a distal flap model, the pathological importance of free radicals in survival of the STSG over a hematoma is insignificant. A more likely hypothesis, as suggested by others, is that a hematoma serves as a barrier preventing angiogenesis.