Myenteric plexus controls gastrointestinal motility by means of well organized circuits which are comprised of sensory neurones, interneurones and motor neurones to the muscular layers. Calretinin (CR) is a calcium-binding protein that, in guinea-pig ileum, has only been found in ascending interneurones, which also express neurofilament triplet proteins (NFT), and excitatory longitudinal muscle motor neurones, which do not. In spite of some evidence that age affects both function and structure of the myenteric plexus, little is known about the possible selectivity of the process regarding specific myenteric neuronal phenotypes. The influence of age on both the structure of the myenteric plexus and the presence of CR-immunoreactive (CR-IR) neurones was studied using conventional immunohistochemical procedures applied to ileal whole-mount preparations from guinea-pigs. Both a reduction in ganglionic size and changes in the distribution of neurones inside and outside the ganglia, together with a general neuronal loss were found in preparations from aged guinea-pigs. More interestingly, a relatively more pronounced age-related loss of CR-IR neurones, especially those lacking of NFT expression, was found. Specific myenteric neuronal phenotypes may show differential sensitivity to ageing, and this could, under certain circumstances, alter the functional balance of gastrointestinal motility in aged individuals.