This study evaluates the effect of direct hemoperfusion (DHP) using polymyxin B-immobilized fibers (PMX-F) as an extracorporeal blood filter on systemic hypotension and lung injury during endotoxemia Sheep were anesthetized, intubated, mechanically ventilated with 50% oxygen and connected to the DHP system between the right femoral artery and left jugular vein. Group 1 (n = 6)sheep were infused with 10 microg/kg Escherichia coli endotoxin over a 30 min period. At the same time, sheep underwent DHP with PMX-F (Toraymyxin: PMX-20R) for 2 h at a flow rate of 60 ml/h. Group 2 (n = 6) sheep were infused with the same dose of endotoxin and treated with a sham column, in the same manner as those in group 1. DHP with PMX-F significantly improved and restored systemic pressure and arterial oxygen tension in group 1 sheep, although these values never returned to the baseline levels of group 2 sheep. Pulmonary hypertension and leukocytopenia were observed after endotoxin infusion in both groups, but there were no significant differences between these values. DHP with PMX-F significantly decreased the elevation of plasma nitric oxide products. The treatment with PMX-F improves shock and deteriorated oxygenation during endotoxemia, probably through the suppression of nitric oxide production.