The potential advantages of high voltage electron microscopy for extending the limits of resolution and contrast in imaging low contrast objects, such as biomolecular specimens, is very great. The results of computations will be presented showing that at accelerating voltages of 500-1000 kV it should be possible to achieve spacial resolutions of 1 to 1.5 Å and using phase contrast imaging achieve adequate image contrast to observe single atoms of low atomic number.The practical problems associated with the design and utilization of the high voltage instrument are, optimistically, within the range of competence of the state of the art. However, there are some extremely important and critical areas to be systematically investigated before we have achieved this competence. The basic electron optics of the column required is well understood, but before the full potential of an instrument capable of resolutions of better than 1.5 Å are realized some very careful development work will be required. Of great importance for the actual achievement of high resolution with a high voltage electron microscope is the fundamental limitation set by the characteristics of the high voltage electron beam that can be obtained from the accelerator column.
