Long-term adrenalectomy (ADX) results in an extensive and specific loss of dentate gyrus granule cells in the hippocampus of adult rats. This loss of granule cells extends over a period of weeks to months and ultimately results in cognitive deficits revealed in a number of tasks that depend on intact hippocampal function. The gradual nature of ADX-induced cell death and the ensuing deficits in cognition resemble in some important respects a variety of pathological conditions in humans. Here, we characterize behavioural and cellular processes, including adult neurogenesis, in the rat ADX model. We also provide experimental evidence for a neurogenic treatment strategy by which the lost hippocampal cells may be replaced, with the goal of functional recovery in mind.