ObjectiveTo present a complementary hypothesis concerning the pathogenesis of the multiple organ dysfunction syndrome.Data SourcesPrimary reports and reviews published in peer-reviewed medical and scientific journals.HypothesisWe suggest that healthy organs behave as biological oscillators, which couple to one another during human development, and that this orderly coupling is maintained through a communications network, including neural, humoral, and cytokine components. We suggest that the systemic inflammatory response syndrome initiates disruption of communication and uncoupling, and further suggest that progression into the multiple organ dysfunction syndrome reflects progressive uncoupling that can become irreversible. Resolution of the inflammatory response and reestablishment of the communications network are necessary but may not be, by itself, sufficient to allow organs to appropriately recouple. This hypothesis is testable using existing laboratory and clinical tools.(Crit Care Med 1996; 24:1107-1116)