Cells are dynamical systems of biomolecular interactions that process information from their environment to mount diverse yet specific responses. A key property of many self-organized systems is that of criticality: a state of a system in which, on average, perturbations are neither dampened nor amplified, but are propagated over long temporal or spatial scales. Criticality enables the coordination of complex macroscopic behaviors that strike an optimal balance between stability and adaptability. It has long been hypothesized that biological systems are critical. Here, we address this hypothesis experimentally for system-wide gene expression dynamics in the macrophage. To this end, we have developed a method, based on algorithmic information theory, to assess macrophage criticality, and we have validated the method on networks with known properties. Using global gene expression data from macrophages stimulated with a variety of Toll-like receptor agonists, we found that macrophage dynamics are indeed critical, providing the most compelling evidence to date for this general principle of dynamics in biological systems.complex systems ͉ normalized compression distance ͉ information theory M any complex systems are capable of undergoing a phase transition between a disorganized and an organized state. This phenomenon has been observed in enzyme kinetics (1), growth of bacterial populations (2), foraging in ant colonies (3), brain activity (4), and traffic flow on the Internet (5). A system that is operating near such a phase transition is said to be critical. At equilibrium, this transition will occur at a critical value of a system parameter, such as the Curie temperature in a ferromagnet, below which the system can maintain spontaneous magnetization. Nonequilibrium systems, however, are capable of selforganizing to such a critical state, whereby complex behavior can emerge in a robust manner without fine-tuning the details of the system (6, 7).A hallmark of critical behavior is the spontaneous emergence of complex and coordinated macroscopic behavior in the form of long-range spatial or temporal correlations. Such coordination across many scales enables information to propagate over time from one part of the system to another with a high degree of specificity and sensitivity. For example, measurements of human brain oscillations revealed such critical dynamics of neural networks, implying their ability to effectively propagate information and rapidly reorganize (8). Similarly, measurements of computer network traffic indicate that the Internet exhibits critical dynamics, accordingly, suggesting optimal information transfer (9, 10). Many other complex systems, such as financial markets (11), forest fires (12), neuronal networks supporting our senses (13), and biological macroevolution (14) have been shown to self-organize to a critical state.A living cell is a complex dynamical system of interacting biomolecules. While this system exhibits stability even in varying environments, it is also capable of changing state...