Dystroglycans are essential transmembrane adhesion receptors for laminin. alpha-dystroglycan is a highly glycosylated extracellular protein that interacts with laminin in the extracellular matrix and the transmembrane beta-dystroglycan. beta-dystroglycan, via its cytoplasmic tail, interacts with dystrophin and utrophin and so to the actin cytoskeleton. As part of the dystrophin-glycoprotein complex of muscle, dystroglycan is also important in maintaining sarcolemmal integrity. Mutations in dystrophin that lead to Duchenne muscular dystrophy also lead to a loss of dystroglycan from the sarcolemma and chimaeric mice lacking muscle dystroglycan exhibit a severe muscular dystrophy phenotype. Here we show, using yeast two hybrid analysis, biochemical and cell biological studies that the cytoplasmic tail of beta-dystroglycan interacts directly with F-actin and furthermore that it bundles actin filaments and induces an aberrant actin phenotype when overexpressed in cells.