Clearance of Pseudomonas aeruginosa from the blood stream in normal dogs was measured. An intravenous infusion of bacteria at a dose of 10(6) per milliliter per minute for two or five hours resulted in reproducible bacteremia in the 10(2) range per milliliter of blood without systemic side-effects. An identical bacterial infusion 24 hours later was characterized by enhanced clearance of bacteria and partial pyrogenic tolerance. A lethal bacterial dose of 4 X 10(7) per milliliter per minute infused for five hours exhibited an eightyfold higher bacteremia, shock and death within 24 hours. These events were characterized by leukopenia, hypothermia and hypoglycemia. Experimental results indicated that intact leukocyte bactericidal activity is the most important defense mechanism of the host in bacterial systemic infections.