There is ample evidence of the involvement of free radicals in mediating skin flap necrosis. Dimethyl sulfoxide (DMSO) is a well-tolerated, safe drug that is a powerful scavenger of the hydroxyl free radical. The current study investigated the effect of DMSO on the survival of 9 x 4 cm skin flaps based on the epigastric vessels subjected to primary venous occlusion. Forty-seven skin flaps were elevated and the epigastric vein was occluded by a microvascular clamp for 8 hours. Group 1 received DMSO (1.5 gm/kg) intraperitoneally at reperfusion. Group 2 received saline solution, group 3 received DMSO at reperfusion and every day for 5 days, group 4 received DMSO preoperatively and then as in group 3, and group 5 was the saline solution control for groups 3 and 4. DMSO did not increase percent flap survival when given as a single dose at reperfusion (40.6% +/- 42.7%) compared with saline solution (33.7% +/- 41.2%). When DMSO was continued in the postoperative period, group 3 (86.2% +/- 25.8%) and group 4 (78.0% +/- 32.5%) had significantly better survival than the saline solution control group (32.6% +/- 39.8%) (p < 0.01 and p < 0.03, respectively). There was no significant difference between groups 3 and 4. DMSO administered at reperfusion and postoperatively for 5 days significantly increased flap survival. It is hypothesized that this occurs through scavenging deleterious free radical species. This effect may have clinical significance.