HAMP domains mediate input-output signaling in histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, and some phosphatases. HAMP subunits have two 16-residue amphiphilic helices (AS1, AS2) joined by a 14- to 15-residue connector segment. Two alternative HAMP structures in these homodimeric signaling proteins have been described: HAMP(A), a tightly packed, parallel, four-helix bundle; and HAMP(B), a more loosely packed bundle with an altered AS2/AS2' packing arrangement. Stimulus-induced conformational changes probably modulate HAMP signaling by shifting the relative stabilities of these opposing structural states. Changes in AS2/AS2' packing, in turn, modulate output signals by altering structural interactions between output helices through heptad repeat stutters that produce packing phase clashes. Output helices that are too tightly or too loosely packed most likely produce kinase-off output states, whereas kinase-on states require an intermediate range of HAMP stabilities and dynamic behaviors. A three-state, dynamic bundle signaling model best accounts for the signaling properties of chemoreceptor mutants and may apply to other transducers as well.