THE present study addressed the hypothesis that the neuronal mineralocorticoid receptor (MR) regulates genes associated with cell death, such as bax and p53, and cell viability, including bcl-2, BDNF, and NT-3. Rats were pretreated with either oil vehicle or the MR antagonist spironolactone (SPIRO) and subsequently injected with saline or kainic acid (KA). MR blockade significantly decreased basal mRNA expression of bcl-2 in CA1 of saline-treated animals and attenuated KA-induced increases in p53 mRNA levels in CA3. SPIRO pretreatment had no significant effect on expression of bax, NT-3, or BDNF mRNAs. The data suggest that the neuronal MR contributes to regulation of select cell survival and cell death-related genes in hippocampal pyramidal neurons.