Extracorporeal membrane oxygenation (ECMO) can provide total cardiopulmonary support via extrathoracic vascular cannulation. We evaluated the effects of ECMO in gram-negative septic shock in immature piglets subjected to fecal-Escherichia coli peritonitis. Group I, SEPSIS CONTROL (n = 10), had an intraperitoneal injection of E. coli but did not receive ECMO. Group II, ECMO CONTROL (n = 5), had 24 hr of ECMO support without the intraperitoneal injection of E. coli, and Group III, ECMO SEPSIS (n = 4), had an intraperitoneal injection of E. coli and was treated with ECMO. In the SEPSIS CONTROL group, mean survival time (+/- SD) was 13.8 +/- 6.3 hr with two survivors to 24 hr. In the ECMO CONTROL group, all five animals survived 24 hr on ECMO and then weaned successfully to conventional ventilatory therapy with return of spontaneous circulation. In the ECMO SEPSIS group, one of the animals died after 22 hr on ECMO and the other three animals died at 24 hr immediately upon withdrawal of ECMO support. Conventional ventilatory therapy was unsuccessful in each. Systemic arterial blood pressure was significantly higher in ECMO CONTROL animals (P less than 0.01) as were leukocyte counts (P less than 0.01). In this model of gram-negative septic shock, ECMO did provide cardiopulmonary support but did not improve mortality.