TGF-β 1 inhibits the cell cycle progression of many types of cells by arresting them in the G 1 phase. This cell cycle arrest has been attributed to the regulatory effects of TGF-β 1 on both the levels and the activities of the G 1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of proteins, such as p15 INK4b, p21 WAF1/Cip1, and p27 Kip1, that physically associate with cyclins, cyclin-dependent kinases (Cdk), or cyclin-Cdk complexes. In epithelial cell lines, TGF-β 1 was previously shown to inhibit cell cycle progression through down-regulation of Cdk4 and/or up-regulation of p15 INK4b and/or p21 WAF1/Cip1. However, TGF-β 1 had little or no effect on the p27 Kip1 mRNA and protein levels. In this report, we show that, in contrast to observations in epithelial cell lines, TGF-β 1 increased the p27 Kip1 mRNA and protein levels in the murine B cell lines CH31 and WEHI231. This TGF-β 1-mediated induction of p27 Kip1 also resulted in an increased association of p27 Kip1 with Cdk2 and a decreased Cdk2 kinase activity. In contrast to epithelial cells, however, TGF-β 1 had little or no effect on the Cdk4 and p21 WAF1/Cip1 protein levels in these B cells. Finally, although several studies suggested a direct role of p53 in TGF-β 1-mediated cell cycle arrest in epithelial cells, TGF-β 1 inhibited cell cycle progression in CH31 even in the absence of wild-type p53. Taken together, these results suggest that TGF-β 1 induces G 1 arrest in B cells primarily through a p53-independent up-regulation of p27 Kip1 protein.