Twenty-three children completed a randomized, prospective, partially blinded study performed to assess the need and effectiveness of antibiotic prophylaxis at the time of burn wound debridement and grafting. Patients with a total body surface area (TBSA) burn less than 35% were randomized to receive cefazolin or placebo. Patients with burns of 35% or more TBSA were randomized to receive cefazolin or targeted antibiotics based on surveillance cultures. Blood cultures were obtained at commencement, immediately after, and 24 hours after surgical debridement. Quantitative cultures and histologic examination of biopsied burn wounds were performed. Burn wound infection occurred in three patients with burns of less than 35% TBSA, two in the cefazolin group and one in the placebo group. Quantitative tissue cultures and histologic examination did not predict either infection. During the four procedures in three patients with 35% or more TBSA, three were randomized to receive cefazolin, and one targeted antibiotics. All receiving cefazolin developed burn wound infection. Quantitative tissue culture was more than 10(5) colony-forming units per gram in all, whereas histologic examination was positive in one. In our patients with less than 35% burn, cefazolin was not necessary, and in those with 35% or more burn, it was not effective.