The indirect immunoperoxidase technique was used to investigate the development of the virus-specific intracellular and cell membrane antigens in cells infected with the Shope fibroma virus. Starting with 6 h p.i., virus antigen formed distinct inclusions within the cytoplasm frequently enclosed by endoplasmic reticulum. The endoplasmic reticulum disappeared almost completely 10 to 12 h p.i., coincidentally with the beginning of virus formation. The virus antigen was distributed throughout the cytoplasm. At the same time virus-induced antigen began to appear at the cell membrane and subsequently increased. No cytochemical staining could be observed on the endoplasmic reticulum, within the nucleus and within immature and mature virus particles. The correlation between antigen synthesis and changes in cell ultrastructure is discussed.