Effects of lidocaine on organ localization of neutrophils and bacteria and on hemodynamic and metabolic variables were determined during septic shock in dogs. Twelve anesthetized dogs were infused with 10(10) Escherichia coli/kg of body weight through a portal vein catheter over a 1-hour period. Six of these 12 dogs were treated with 2 mg of lidocaine HCl/kg (6 mg/kg/h) 15 minutes after the bacterial infusion had begun. Six dogs not given E coli (surgical controls) were given saline solution at the same rate as the bacterial and lidocaine infusions. Over 4 hours, nontreated dogs with septicemia developed systemic hypotension, decreased cardiac output, increased portal pressure, increased serum alanine transaminase activity, increased liver extravascular water, increased liver glycogen depletion, and decreased PaO2, compared with control dogs. Accumulations of polymorphonuclear leukocytes and E coli were found in the liver and lungs of dogs with septicemia. Lidocaine treatment did not alter the hemodynamic measurements and resulted in metabolic acidosis and hypoalbuminemia. Decreased numbers of E coli were recovered from the liver of lidocaine-treated dogs, whereas increased numbers of organisms were recovered from the blood. Neutrophil sequestration was increased in the liver, but not the lungs of lidocaine-treated dogs.