We evaluated the effects of SK&F 86002, a dual 5-lipoxygenase/cyclooxygenase inhibitor, on the responses to 30 mg/kg Escherichia coli endotoxin (bacterial lipopolysaccharides, LPS) in conscious male Sprague-Dawley rats. Injection of LPS increased serum tumor necrosis factor (TNFα) activity from 20 U/ml (baseline) to 1,066 ± 430 and 2,825 ± 1,155 U/ml (n = 9) at 30 min and 1 h after administration of LPS, respectively (p < 0.01 as compared with the vehicle control group). This dose of LPS reduced the survival rate to 99? at 48 h (mean survival time 9.7 ± 2.7 h), increased heart rate (HR) to 494 ± 18 beats/min, increased the hematocrit to 56 ± 2 vol%, reduced the circulating platelet count at 6 h to 409? of the initial value, and produced leukopenia of 309? of the initial value at 1 h, with recovery to the initial value at 6 h. Administration of 30 mg/kg SK&F 86002 (intragastric, i.g.) 1 h before injection of LPS reduced serum TNF“ concentrations to 92 ± 58 and 184 ± 117 U/ml at 30 min and 1 h (p < 0.05), respectively, and also reduced the hemoconcentration. The survival rate was improved to 60% (mean survival time 38.1 ± 4.3 h; p < 0.05), although there was no effect on the hemodynamic responses to LPS. SK&F 86002 significantly reduced thrombocytopenia at 30 min and 1 h (p < 0.05), but not at 3 and 6 h, and had no effect on changes in white blood cell (WBC) count. SK&F 86002 at a dose of 10 mg/kg i.g. was less effective at inhibiting the increase in serum TNFα activity. the change in hematocrit, or the decrease in survival rate, indicating that the effects of SK&F 86002 were dose dependent. These results indicate that administration of SK&F 86002 dose-dependently attenuated the increase in serum TNFα concentrations, and this response was associated with a corresponding improvement in the survival rate of endotoxemic animals