Human synovium is richly innervated by autonomic and sensory nerve fibres, many of which contain neuropeptides. The hypothesis is that, in addition to a sensory role, some of these fibres modulate the response of the synovial membrane to a variety of noxious stimuli by releasing these peptides. Synovial damage results in acute inflammation in the damaged joint and a neurogenically mediated infiltrate of inflammatory cells in the contralateral joint. These cells might protect the contralateral synovium from injury similar to that in the damaged joint. An increased response would lead to synovitis and symmetrical disease.