It is known that there is an age-related increase in gastrointestinal diseases. However, there is a lack of studies dealing with the correlation between age-related changes in function and intrinsic innervation in the gastrointestinal tract. The purpose of this work was to study this subject in the guinea pig ileum, whose functional and structural features are well known in the young age. Ileal longitudinal muscle -- myenteric plexus (LMMP) preparations were obtained from 3-to 24-month-old guinea pigs. Both functional and immunohistochemical techniques were applied. The force of the contraction elicited by excitatory stimuli (electrical stimulation, acetylcholine, substance P, and opioid withdrawal) increased in parallel with an age-dependent reduction in the density of excitatory motor neurones to the longitudinal muscle, whereas other subpopulations of neurones, including inhibitory motor neurones, decreased much more slowly. Although the increase in responsiveness could be related to the age/weight-related increment in muscle bulk, some compensatory modifications to the lowered density of excitatory neurones could also be involved. On the other hand, the acute inhibitory response to morphine remained unaltered in old animals, whilst in vitro tolerance was lower. These results suggest that although age-dependent neuronal loss does not cause dramatic changes in intestinal motility, it is a factor that could contribute to disturbing normal responsiveness and, perhaps, underlie the higher frequency of gastrointestinal diseases encountered in the elderly.