The complement (C) inhibition caused by bacterial endotoxin is well known, but the relationship of this reaction to endotoxin shock is unclear. Anesthetized dogs were therefore given Escherichia coli endotoxin intravenously with or without prior C depletion by a purified cobra venom factor (CVF). Mean aortic blood pressures (MAP) and C levels were measured. Intravenous CVF usually caused an early transient drop of MAP and a profound, long-lasting drop in C. Bacterial lipopolysaccharide (LPS) alone always caused a sudden (within 2 min) drop in MAP which was followed by partial recovery and then more long-lasting depression. Moderate drops in C usually occurred. In animals pretreated with CVF so that C levels were markedly depressed (<25% of control), LPS did not elicit the immediate MAP drops; however, a later (after 5 to 20 min) MAP drop always occurred. CVF pretreatment did not modify LPS-induced mortality. CVF effects were not caused by LPS contamination. These data show that the early hemodynamic responses of the dog to LPS may be mediated through the complement system.