We developed a model of lesion of Schaffer collaterals in hippocampal organotypic slice cultures to analyse the capacity for sprouting and functional recovery expressed in young (one week old) and old (four week old) slice cultures. Slice cultures were sectioned at different ages of maturation in two separate half-slices and maintained in co-culture. Functional recovery was assessed by measuring synaptic responses elicited across the lesion seven days after the lesion and sprouting was evaluated by biocytin labeling of the regenerating fibers seen under the same conditions. Sprouting and functional recovery were found to be markedly reduced and delayed in old vs young cultures. Preparation of co-cultures between young CA3 and old CA1 half-slices resulted in a significant reduction in the capacity for sprouting and regeneration of the young CA3 neurons. Conversely, co-cultures prepared between old CA3 and young CA1 half-slices showed a markedly enhanced capacity for sprouting and functional recovery of old CA3 neurons. These results indicate that the age-dependent impairment in sprouting and regeneration expressed in cortical regions can be improved by and depends upon the presence of a favourable environment.