To determine if and when intussusception results in endotoxemia and to evaluate whether diagnostic and surgical interventions of intussusception aggravate endotoxemia, intussusception was created in seven pigs during general anesthesia (ileocolic n = 3, ileo-ileocolic n = 2, ileocolic with silicone ring as leadpoint n = 1, ileoileal with silicone ring n = 1). After a period of observation and before progression to bowel gangrene, a diagnostic ultrasound study with a saline enema was undertaken, followed by a laparotomy and resection of the intussusception with a primary bowel anastomosis. Serial blood samples were obtained before and at regular intervals after: (1) formation of the intussusception; (2) the enema; and (3) resection for endotoxin measurement by limulus amebocyte lysate assay. The mean level of endotoxin increased from a pre-intussusception value of 0.750 EU/ml (range: 0.215-1.281) to a post-intussusception maximum of 1.482 EU/ml (0.997-2.882, P = 0.009), peaking mostly at 2 h after the intussusception. The mean pre-saline-enema level was 1.547 EU/ml (0.869-2.677) while the post-enema level was 1.41 EU/ml (0.84-2.468, P = 0.655). The mean pre-resection level was 1.470 EU/ml (0.784-2.468) while the post-resection maximum was (2.130 EU/ml) (0.850-4.381, P = 0.09). It is concluded that: (1) even in the absence of bowel gangrene intussusception results in significant endotoxemia within 2 h of its formation; (2) gentle saline enemas are not associated with endotoxemia; and (3) surgical resection results in a further upward surge of endotoxemia. These findings provide a scientific basis for improved understanding and management of intussusception.