The Young's modulus of cultured mouse and rat vascular smooth muscle cells (VSMC) was measured with an atomic force microscope (AFM). The AFM can image the three-dimensional structure of biological cells in a physiological environment enabling real-time biochemical and physiological processes to be monitored at a resolution similar to that obtained for the electron microscope (EM). Cellular mechanical properties were determined by indenting the cell's body, and analyzing the indentation data with classical infinitesimal strain theory. This calculation was accomplished by modeling the AFM probe as a cone. as well as a blunted cone. The blunted cone geometry fits the AFM force indentation data well and was used to calculate the Young's Modulus (E) of the respective VSMC cell body under various conditions. HEPES, a buffer solution commonly used to maintain pH in culture was found to alter the Young's Modulus (E) and the morphology of rat cells. Old mouse VSMCs had a higher Young's Modulus (E) than younger ones, with a clear change in cytoskeleton morphology. A change in cell body morphology was seen after application of drug, treatment.