Confocal microscopy is a valuable adjunct to electron microscopy in the fields of diagnostic and investigative virology. Confocal imaging can be used to examine large amounts of tissue stained by a variety of methods for evidence of viral infection. Areas thus identified can then be processed for ultrastructural study, allowing a highly focused search for viral pathogens. With the possible exception of the vibrating microtome, all of the equipment and reagents necessary for the preparation of specimens for confocal scanning are available in any well-stocked histology laboratory. Although originally developed to facilitate viral diagnosis by EM, the methods described herein can be applied to the ultrastructural study of any focal pathologic process.