Interactions between the indigenous flora of the gastrointestinal tract and immunologically competent cells in the gut mucosa, gut-associated lymphoid tissues and liver play an important role in normal immune homeostasis. The microbial flora of the normal gut is complex, yet remarkably constant over time. The relative sterility of the upper gut is maintained by multiple factors including gastric acid, bile salts, normal motility and mucosal IgA, while the lower gut is densely colonized with a complex flora. An intact Gram-negative flora is a prerequisite for normal immunological maturation. On the other hand, overgrowth of the gut, particularly by Gram-negative bacteria or fungi, facilitates the translocation of bacteria into the host, and results in suppression of T-cell responses and altered hepatic Kupffer cell function. Bacterial overgrowth and the consequences of the interactions of this potentially pathogenic flora with the gut immune system may contribute to the septic state in critical illness, and to the syndrome of multiple organ failure.