It has previously been reported that several octamer binding transcription factors including the Oct-2 factor can repress the involucrin gene promoter in keratinocyte cells. As the Oct-2 factor exists in several different cell type-specific isoforms with distinct activating or inhibiting effects on gene expression, we have tested the effect of these forms on the involucrin promoter. We report here that at high concentrations each of these isoforms can inhibit theinvolucrin promoter in keratinocytes. In other cell types however, all three isoforms activate the involucrin promoter and this effect is also observed at low concentrations of Oct-2 in keratinocytes. The mechanisms responsible for these effects are discussed.