To test the hypothesis that nonselective adsorption by a hydrophobic resin of cytokines and other proinflammatory mediators could improve 72-hr survival in a rabbit model of endotoxic shock. Prospective, randomized, controlled animal trial. Animal care facility at a research institution. A total of 109 New Zealand white male rabbits. Anesthetized rabbits were cannulated with indwelling femoral arterial and venous lines. Septic shock was induced by a single intravenous injection of Escherichia coli lipopolysaccharide. The dose was experimentally assessed in 40 rabbits receiving 1.0, 0.5, 0.1, and 0.05 mg/kg body weight to determine LD80 at 72 hrs. Extracorporeal circulation consisted of plasma filtration coupled with passage of the plasma filtrate through a hydrophobic sorbent and reinfusion into the venous line. The extracorporeal treatment lasted for 3 hrs. Rabbits injected with endotoxin (0.05 mg/kg) were submitted to plasma filtration with (19 rabbits) or without (20 rabbits) sorbent adsorption. As controls, rabbits injected with vehicle alone were treated with plasma filtration (ten rabbits) or without (ten rabbits) sorbent adsorption. Ten rabbits were monitored under anesthesia to determine basal survival. Plasma concentrations of endotoxin, bioactive tumor necrosis factor, resin-adsorbed platelet-activating factor, mean arterial pressure, base excess, and white cell count were assessed and a global severity score was established. At 72 hrs, cumulative survival was significantly (p = .0041) improved in septic rabbits treated with coupled plasma filtration-adsorption. Circulating tumor necrosis factor bioactivity remained similar in control and treated rabbits. Biologically significant amounts of platelet activating factor were eluted from the sorbent during the entire treatment time. The severity score inversely correlated with survival (p < .001). Coupled plasma filtration-adsorption improved survival in a rabbit model of endotoxic shock. Coupled plasma filtration-adsorption may be an extracorporeal treatment capable of removing structurally different inflammatory mediators associated with sepsis.