We determined whether plasma levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) accurately reflect the tissue GSH and GSSG levels in lung and liver during a progressive acute inflammation-induced increased oxidant activity. We also determined whether plasma GSH also reflected other antioxidant defenses. Male Wistar rats (n = 38) were given intraperitoneal zymosan (.75 mg/g body weight) producing an acute progressive peritonitis and generalized inflammation. Animals were resuscitated then killed at 4 or 24 h. Plasma and tissue levels of GSH, GSSG, vitamin C, alpha-tocopherol, and catalase were measured. Conjugated dienes and malondialdehyde were used as tissue markers of lipid peroxidation. We found lung and liver tissue GSH to be decreased significantly at 4 h while GSSG was increased. Lipid peroxidation was also present in the lung. At 24 h, GSH remained decreased in liver and GSSG remained increased in lung along with the lipid peroxides conjugated dienes and malondialdehyde. In addition, overall antioxidant defenses were decreased in both lung and liver. Plasma GSH remained decreased at 24 h corresponding with the decrease in liver GSH as well as the decrease in other plasma and tissue antioxidants. However, plasma GSSG levels were not significantly increased, at any time point, indicating plasma GSSG does not accurately reflect tissue oxidant activity.