Based upon the prior observation that drugs which reduce sympathetically induced lipolysis also reduce plasma volume loss following thermal trauma, it was postulated that the products of the metabolism of polyunsaturated fatty acids (PUFA) were the substances causing the plasma volume loss. The two major metabolic pathways for PUFA are cyclo-oxygenase transformation to form prostaglandins and lipoxygenase transformation to form fatty acid hydroperoxides. This latter pathway also produces the superoxide anion and hydrogen peroxide. To test the effects of alterations of these pathways of PUFA metabolism upon plasma volume loss, the effects of indomethacin (a cyclooxygenase inhibitor), orgotein (a superoxide dismutase), and catalase (an enzyme which converts hydrogen peroxide to inactive substances) were studied in anesthetized dogs receiving a 15% total body surface area third-degree flame burn. The results of this study showed that indomethacin did not alter postburn plasma volume loss, orgotein reduced early plasma volume loss but did not reduce continuing loss, and catalase reduced both early and continuing plasma volume loss.