The three mammalian isoforms of transforming growth factor-β (TGF-β1, β2, β3) are potent regulators of cell growth, differentiation, and extracellular matrix deposition. To study their role in skin differentiation, we investigated the expression of TGF-β isoforms on cell growth and differentiation induction of the human keratinocyte cell line, HaCaT by elevating the Ca 2+ concentration. An ELISA and RT-PCR assay revealed secreted TGF-β1 protein and TGF-β1 mRNA were increased during calci-um-induced differentiation. In contrast, major differences were seen for TGF-β2 and TGF-β3 mRNA which were decreased during differentiation, but TGF-β2 and TGF-3β protein were not evident on an ELISA. These results suggest different functions for each TGF-β isoforms in epidermal differentiation, such that TGF-β1 is associ-ated with the more differentiated state, and TGF-β2 and TGF-β3 may be associ-ated the more proliferated state.