Thanks to electron microscopy, the modern cytologist has a clear and beautiful picture of the normal cell. The fine structure of the cell's various organelles has been revealed (1, 2), classical controversies have been settled (3, 4), and a representation of cellular submicroscopic organization has been denned in a universal manner (5, 6). The validity of the morphologic results thus attained has been established. In contrast to the opinions prevalent only 5 years ago, no one will deny this any longer since truly satisfactory methods of tissue preservation have been devised, which can be judged by comparison with phase contrast pictures of living cells.

But the situation is quite different when pathology and cancer, in particular, are concerned. Either no real difference between the ultra-structure of cancerous cells and that of normal cells was observed, or cellular lesions, when present, could not be related with certainty to an etiologic factor (7-10).

It is the purpose of this brief survey to re-evaluate, after the passage of many years of extensive search, the worth of ultrastructural morphology as a tool in cancer research.

Virus-induced tumors will be given special consideration because these growths appeared at first ideally fitted to studies with the electron microscope, since cancer is a cellular disease, and viruses could be observed visually for the first time. Yet, despite the remarkable observations of particles in Rous sarcoma cells and in cells of mouse mammary tumors, by Claude, Porter, and Pickels (11) and Porter and Thompson (12), further demonstration of viruses in viral tumors was long delayed and these early discoveries could not be substantiated for many years.

During these periods of difficulties and struggle, investigators realized the importance of detecting indirect signs of viral involvement in the affected cells, since direct evidence of virus particles was difficult to obtain. The first part of this report will deal with the search for such signs. Another necessity was for the electron microscopist to develop systems in which virus particles multiply and reach higher intracellular concentrations than under natural conditions. This will be the subject of the second part of the present report.