We studied the effect of the topical application of the nonsteroidal anti-inflammatory agent, flurbiprofen, on postburn hypermetabolism and systemic lipid peroxidation. Twelve sheep with a 15% total body surface third-degree burn were monitored over a 4-day postburn period. In six sheep, a single application of a 5% flurbiprofen cream was placed on the burn wound on day 3. Data were compared to both burned and nonburned controls (n = 6). All animals were killed on day 4. Oxygen consumption was increased at day 3 by 28% +/- 10% over the preburn value in all animals. Flurbiprofen significantly attenuated the increase in oxygen consumption, returning the value essentially to baseline by 12 hours after application. Lung and liver peroxidation, as measured by malondialdehyde, was significantly increased in the burned, nontreated sheep at day 4 from a control value of 45 +/- 9 and 110 +/- 12 to 60 +/- 6 and 310 +/- 71 nmol/gm tissue, respectively. In flurbiprofen-treated animals, values were 42 +/- 8 and 160 +/- 18 nmol/gm at day 4, significantly attenuated from burn alone. Protein-rich burn lymph flow remained fourfold increased in both groups, indicating a persistent increase in burn tissue vascular permeability, not modified by flurbiprofen. Burn wound biopsies revealed bacterial contents of less than 10(4) organisms/gram tissue in all animals. We conclude that topical flurbiprofen significantly decreases burn wound-induced systemic hypermetabolism and oxidant-induced lipid peroxidation seen at 3 days after burn injury, but does not attenuate the remaining local burn-wound vascular permeability.