Transforming growth factor-beta (TGF-ß) can induce epithelial to mesenchymal transdifferentiation (EMT) in mammary epithelial cells. TGF-ß-meditated EMT involves the stimulation of a number of signaling pathways by the sequential binding of the type II and type I serine/threonine kinase receptors, respectively. Integrins comprise a family of heterodimeric extracellular matrix (ECM) receptors that mediate cell adhesion and intracellular signaling, hence making them crucial for EMT progression. In light of substantial evidence indicating TGF-ß regulation of various ß1 integrins and their ECM ligands we examined the cross talk between the TGF-ß and integrin signal transduction pathways. Using an inducible system for the expression of a cytoplasmically truncated dominant-negative TGF-ß type II receptor (DNIIR), we blocked TGF-ß-mediated growth inhibition, transcriptional activation, and EMT progression. DNIIR expression at maximal levels inhibited TGF-ß signaling to the SMAD and AKT pathways, but did not block TGF-ß-mediated p38MAPK activation. Interestingly, blocking integrin ß1 function inhibited TGF-ß-mediated p38MAPK activation and EMT progression. Limiting p38MAPK activity through the expression of a dominant negative-p38MAPK also blocked TGF-ß-mediated EMT. In summary, TGF-ß-mediated p38MAPK activation is dependent on functional integrin ß1, and p38MAPK activity is required but is not sufficient to induce EMT.