One of the primary goals of scanning tunneling microscopy (STM) work in biology is to obtain high-resolution images of biological molecules under conditions that resemble those in vivo. To accomplish this goal two main difficulties need to be overcome. (1) Problems caused by the low conductivity of biological material, and (2) depositing the sample in a controlled and reliable way on a flat, inert conducting substrate. The first problem can be solved by coating the sample with a thin metal layer, at some cost in resolution. This allows the second problem, controllable depositing the sample, to be approached systematically, independent of difficulties caused by low conductivity. Using this approach, two different kinds of viruses have been imaged, bacteriophage T7 and fd. STM images of intact T7 and fd bacteriophages, and lysed T7 phages have been obtained in a straightforward and routine way. To obtain high-resolution images it is necessary to use uncoated samples. The conductivity problems cannot be avoided in this case, but they can be minimized by using thin samples. We have been able to obtain STM images of uncoated DNA molecules with about 10 A resolution, in a variety of packing arrangements and conformations. One conclusion resulting from these experiments is that the STM tip often makes contact with uncoated molecules and sweeps them aside rather than imaging them. The mechanism of conduction through the DNA, and methods by which the tip contact problem can be overcome are discussed. © 1990, American Vacuum Society. All rights reserved.