During the last 6 years, 19 infants with sepsis have been treated with exchange blood transfusions 47 times, and 13 patients survived. However, this procedure is compromised by antibody formation against WBCs and platelets. Accordingly, a miniature system for on-line plasma exchange (PE) between septic infant and healthy parent has been developed and evaluated using a canine model. Escherichia coli, at a dose of 5 X 10(9) CFU/ml/kg, was injected intravenously into 17 puppies that were divided into 3 groups; untreated; sham treated; and PE in which 80 ml/kg of plasma in each septic puppy was replaced during 2 hr with fresh plasma simultaneously obtained from healthy adult dogs. Four of 5 puppies survived in the PE group, while all other puppies died within 24 hr. In the PE group, viable cell counts of E. coli and endotoxin decreased significantly, and opsonic activity improved. This system is effective and applicable for treatment of sepsis in infants.