Taste receptor cells utilize the cAMP and other second messenger systems in transducing sweet and bitter stimuli into physiological responses. However, long-term consequences of taste stimulation, such as gene expression, are unknown. We investigated the presence of cAMP response element-binding protein (CREB), a stimulus-induced transcription factor, in taste receptor cells. Using immunocytochemistry, both CREB and its activated form, phosphorylated-CREB (pCREB), were localized to a subset of rat taste receptor cells. Basal level of pCREB was high in the absence of any known stimulation. Using western blot analysis and specific protein kinase inhibitors, CREB phosphorylation was demonstrated to be linked to protein kinase A but not to protein kinase C activation. Stimulation of taste receptor cells with sucrose, a sweet stimulus that elevates cAMP levels, was without effect on CREB phosphorylation. There was a tendency for quinine stimulation, a bitter stimulus that lowers cAMP, to reduce CREB phosphorylation. These results suggested that taste receptor cells express CREB and that its phosphorylation is influenced by the cAMP second messenger system.