We have developed a method for measuring the local deformability by indentation of individual cells adherent to a rigid substratum. The measured cellular stiffness is dominated by the actin cytoskeleton. This method provides a procedure by which the physiological function of a cytoskeletal protein can be assayed in a living cell. A recent application of this idea is illustrated in recent studies of the function of the protein dystrophin, the absence of which is responsible for Duchenne muscular dystrophy, a severe muscle degenerative disease. The protein is large (427 kD). Its structure suggests that its function is to link the cortical actin cytoskeleton within a muscle cell to the extracellular matrix outside the cell. This is thought to provide mechanical stabilization for the muscle cell membrane during contraction. This hypothesis on dystrophin function predicts that muscle cells which lack dystrophin should be less stiff than those which have the protein. This hypothesis was recently verified by comparing measurements of the indentational stiffness of muscle cells from control normal mice and from mice which lack dystrophin and provide a good model for Duchenne muscular dystrophy. Figure 1 illustrates the difference between typical indentational stiffness measurements of normal and dystrophin-deficient cells. Measurements of this type verify the hypothesis that the absence of dystrophin causes a substantial softening of the cell.