Tau proteins are encoded by a single gene which is regulated by a unique promoter. The proximal 196 base pairs of the tau 5' flanking region confers tau protein with neuronal specific expression and nerve growth factor inducibility. We tested tau promoter activity in neuronally differentiated embryonal carcinoma cells, the P19 mouse blastoderm cell line. In these experiments, we examined the temporal expression pattern of the tau promoter and compared it to other viral and cellular promoters. Tau promoter activity increases significantly with differentiation, specifically during neurite initiation. In addition, tau promoter activity in neuronally differentiated P19 cells was significantly greater than all five of the other neuronal or non neuronal promoters tested. All other promoters displayed low levels of promoter activity throughout retinoic acid induced neuronal differentiation of P19 cells. Taken together, our results suggest that the tau promoter is a good choice for ectopic expression of exogenous genes in P19 cells, which serves as a differentiating neuronal model system.