Serotonin type-3 (5-HT3) receptors are cation permeable membrane receptors which are involved in modulation of calcium entry in neuronal cells. Along with other ion-channels such as the N-methyl-D-aspartate receptor, it appears to be a target for the actions of ethanol and has been the focus of considerable work in this regard. Since in animals, ethanol exposure results in elevations of corticosteroids in both acute and chronic conditions, we studied the effects of both ethanol and corticosteroid exposure on 5-HT3 gene expression in an in situ pheochromocytoma-12 (PC12) cell model. We found that ethanol exposure alone (80 mMx4 days) did not significantly alter target gene expression. Corticosterone (CORT) (50, 150, and 300 ng/ml) resulted in significant increases in 5-HT3 expression which were attenuated by mifeprestone (50 ng/ml). Ethanol in combination with CORT did not significantly alter the increase in 5- HT3 mRNA seen with CORT alone. We conclude that in PC12 cells, exposure to CORT at physiologically relevant concentrations increases 5-HT3 gene expression.