Glucocorticoid excess is associated with hippocampal neuronal dysfunction and loss, mainly affecting CA1. Degeneration of both cholinergic and serotonergic (5-HT) hippocampal afferents is prominent in aged rats and Alzheimer's disease. Lesions of these individual pathways alter hippocampal expression of mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNAs; both transcripts are increased by cholinergic lesions, but markedly decreased by serotonergic denervation. In the present study we found that combined medial septal cholinergic and central 5-HT lesions increase hippocampal GR mRNA expression, specifically in CA1 and CA2 subfields, whereas MR mRNA expression was similar to controls. Thus the effects of the cholinergic lesion, at least upon GR gene expression, appear to predominate while the effects of the lesions upon MR gene expression were additive. Increased hippocampal GR gene expression per neuron may increase hippocampal neuronal vulnerability with age or disease.