The activities of choline acetyltransferase and acetylcholinesterase were determined in 5 consecutive septo-temporal regions of the ipsilateral and contralateral hippocampus from unlesioned controls and lesioned animals at various times following lateral, medial or complete unilateral transection of the fimbrial bundle in rats. In control animals distribution of cholinergic enzymes suggests a relatively heavier innervation of the ventral hipocampus. In lesioned animals depletion of enzyme activities in septo-temporal regions of the ipsilateral hippocampus was consonant with the known topography of cholinergic innervation of the hippocampus via the dorsal and ventral pathways. After 4 and 8 wk post-lesion survival, a substantial recovery of both enzyme activities was evident following either of the lesion paradigms employed. The extent and the pattern of enzyme restitution depended on the type of fimbrial transection and the hippocampal region under consideration. Significant enzyme alterations were also observed in the contralateral hippocampus following all 3 lesion types. The lesion-induced temporal consequences in cholinergic enzymes apparently indicate initial degeneration and subsequent regeneration of cholinergic terminals in the hippocampus. Homologous fimbrial fibers spared by the partial lesions may be responsible for the ensuing recovery. Partial lesions of well-defined efferents constitute a suitable experimental paradigm to demonstrate homotypic reconstruction in the adult mammalian CNS.