Motile E. coli cells use transmembrane chemoreceptors to track chemical gradients with extraordinary precision. The receptors form cooperative, supramolecular arrays through interaction with an autokinase, CheA, and a scaffold protein, CheW, that couples CheA activity to receptor control. This “three-protein brain” produces signals that control the cell’s flagellar motors in response to chemical stimuli. My lab uses molecular genetic approaches to investigate how stimulus information travels through the chemotaxis signaling proteins, the sources of signal amplification in the system, and the mechanisms of CheA kinase control. My talk will present some of the evidence for our current molecular view of signal transduction in the E. coli chemotaxis system.