To determine whether parenteral L-arginine supplementation enhances the impaired wound healing of rats subjected to trauma/hemorrhagic shock. Impaired wound healing after trauma and shock has been documented experimentally and clinically. L-arginine has been shown to enhance wound strength and collagen synthesis in rodents and humans. Its efficacy under conditions of impaired wound healing is less well defined. Forty-eight male Lewis rats were used in this study. Using a well-defined model, 24 rats underwent trauma/hemorrhagic shock before wounding. Twenty-four untreated rats served as controls. All animals underwent a dorsal skin incision with implantation of polyvinyl-alcohol sponges. Half of the animals in each group were assigned to receive 1 g/kg/day of L-arginine by intraperitoneal injection in three divided doses, while the other half received saline injections only. Animals were sacrificed 10 days postwounding, and wound-breaking strength (WBS) and wound sponge total hydroxyproline (OHP) and nitrite/nitrate (NO(x)) content were determined. Wound sponge RNA was collected and subjected to Northern blot analysis for procollagens I and III. Trauma/hemorrhage greatly decreased WBS with a concomitant diminution in collagen (OHP) deposition. L-arginine significantly enhanced WBS (19%) and increased OHP (21%) levels in control animals as well as in rats subjected to trauma/hemorrhage (WBS +29%, OHP 40%) compared with their saline-treated counterparts. Procollagen I and III mRNA levels were elevated by L-arginine treatment in both trauma/hemorrhage and control rats. Arginine treatment had no effect on wound fluid and plasma NO(x). The data demonstrate that the impaired healing subsequent to trauma/hemorrhage can be greatly alleviated by L-arginine supplementation.