It has previously been shown that adrenalectomy (ADX) produces apoptosis in the granule cell of the dentate gyrus (DG), and that this effect is prevented by corticosterone replacement. Thus, we have investigated how this phenomenon takes place in rat hippocampus using in situ hybridization. The expression of the pro-apoptotic gene bax was measured in the pyramidal cell fields and in the DG. After 5 days of ADX, there was a significant increase in bax mRNA levels in the suprapyramidal layer of the DG, an effect prevented by corticosterone replacement. The mRNA of the anti-apoptotic bcl-2 gene was expressed in CA3 and DG. ADX increased bcl-2 mRNA levels, but only in the suprapyramidal layer of the DG, an effect that was prevented by corticosterone administration. It is concluded that the up-regulation of bax may explain the apoptosis observed in DG after ADX, while the bcl-2 induction may correspond to a compensatory mechanism protecting the cells from death.