The peptide neurotransmitter substance P modulates sensitivity to pain by activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete populations of neurons throughout the central nervous system [1-4]. Substance P is synthesized by small-diameter sensory 'pain' fibres , and release of the peptide into the dorsal horn of the spinal cord following intense peripheral stimulation  promotes central hyperexcitability and increased sensitivity to pain [7-10]. However, despite the availability of specific NK-1 antagonists , the function of substance P in the perception of pain remains unclear. Here we investigate the effect of disrupting the gene encoding the NK-1 receptor in mice. We found that the mutant mice were healthy and fertile, but the characteristic amplification ('wind up') and intensity coding of nociceptive reflexes was absent. Although substance P did not mediate the signalling of acute pain or hyperalgesia, it was essential for the full development of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpected role in the adaptive response to stress.