Periodontal ligament (PDL) is a specialized connective tissue that influences the lifespan of the tooth. Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine, but little is known about the effects of TGF-beta 1 on PDL cells. Our aim has been to demonstrate the expression of TGF-beta 1 in rat PDL tissues and to evaluate its effects on the proliferation and gene expression in human PDL cells (HPLCs) and a human PDL stem/progenitor cell line, line 1-11, that we have recently developed. The expression of TGF-beta 1 in the entire PDL tissue was confirmed immunohistochemically, and both HPLCs and cell line 1-11 expressed mRNA from the TGF-beta 1, TGF-beta type I receptor, and TGF-beta type II receptor genes. Although exogenous TGF-beta 1 stimulated the proliferation of HPLCs, it did not upregulate the expression of alpha-smooth muscle actin (alpha-SMA), type I collagen (Col I), or fibrillin-1 (FBN 1) mRNA or of a-SMA protein in HPLCs, whereas expression for these genes was attenuated by an anti-TGF-beta 1 neutralizing antibody. In contrast, exogenous TGF-beta 1 reduced the proliferation of cell line 1-11, although it upregulated the expression of alpha-SMA, Coil, and FBN 1 mRNA and of alpha-SMA protein in this cell line. In addition, interleukin-1 beta stimulation significantly reduced the expression of TGF-beta 1 mRNA and protein in HPLCs. Thus, TGF-beta 1 seems to play an important role in inducing fibroblastic differentiation of PDL stem/progenitor cells and in maintaining the PDL apparatus under physiological conditions.