Following peripheral-nerve lesions there are well-documented events that affect the contralateral nonlesioned structures. These contralateral effects are qualitatively similar to those occurring at the ipsilateral side, but are usually smaller in magnitude and have a briefer time course. It is unclear whether the findings are an epiphenomenon or serve a biological purpose, but in either case the existence of these effects implies the presence of unrecognized signalling mechanisms that link the two sides of the body. Strong circumstantial evidence argues against a peripheral mechanism (for example, via circulating factors) and in favour of a central mechanism, in particular signalling via the system of commissural interneurons that is present in spinal cord and brainstem. While an altered pattern of activity in this system might underlie the phenomenon, there are several reasons for proposing that the changes depend upon chemical signals, possibly growth factors. Because of its relative easy access for experimental manipulation, the spinal cord could serve as a model system to study these transmedian signalling systems.