The resolution of many questions concerning the mechanism and the regulation of tissue cell motile phenomena can be approached only when additional structural data becomes available. It is doubtful that conventional thin-section electron microscopy will be adequate to provide the required information. In the proposed research imaging of whole critically point dried cells in the High Voltage Electron Microscope (HVEM) will be used to provide a detailed and quantitative description of the distribution of microtubules, microfilaments and 100 A filaments within cells and the spatial relationship of these fibers to cytoplasmic organelles and to the interior of the cell surface. Stereo electron microscopy will be used to provide a three-dimensional reconstruction of internal cell morphology and to determine the points of cell-to-substrate contact. In the basic experimental protocol animal cells, grown on Formvar-coated electron microscope grids, will be monitored by time-lapse photography in the light microscope and processed for whole-mount viewing after perfusion-fixation to arrest a particular motile event. The possible association of a distinct fiber pattern, revealed in the HVEM, with a discrete unit of cell behavior will be tested by comparative analysis with the film record of the same cell observed in the living state.