Two fibre systems converge upon the medial nucleus of the septum, and these have been studied at the electron microscopic level in the adult rat. Applying the method of orthograde fibre degeneration reveals that fimbrial fibres terminate on dendrites only, whereas the hypothalamic fibres terminate on cell somata as well as dendrites. At longer survival times after a lesion the degenerating fragments are completely removed, but a permanent plastic change is found. Thus, if a long-term lesion is made in one fibre system, a second short-term lesion placed in the other system reveals that the distribution of the second system has been modified in response to the original de-afferentation. After long-term fimbrial lesions, this modification takes the form of axon terminals contacting an unusually high number of dendritic profiles. Conversely, after a long-term lesion of hypothalamic fibres, it is found that fimbrial fibres now occupy terminal sites on cell somata. Both observations suggest a re-occupation of de-afferented sites by local intact terminals. Such a process must entail at least a partial loss of growth specificity. The rapid re-occupation of sites by local heterotypic terminals may remove an important stimulus for the re-growth of the original cut axons and may thus be a factor in the apparent failure of effective anatomical regeneration in the central nervous system.