Abstract Human foreskin cells exposed to SV40 exhibited characteristic cytopathic changes as early as 2 days after infection. The changes, occurring much sooner than in other reported human cells, included enlargement of nuclei and nucleoli, formation of multiple eosinophilic nuclear inclusions, and basophilic RNA-containing bodies in the cytoplasm. The nuclei showed bright fluorescence of various patterns with the indirect Coons' method. During the following days cell destruction occurred simultaneously with increased cell proliferation. Foci of rapidly dividing transformed cells appeared 3–4 weeks after infection. The transformed cells also differed from untransformed cells in morphology and growth pattern, showing many abnormal mitoses, and were more easily suspended by trypsinization. Virus was released, but in decreasing amounts, with serial passage of the transformed cell cultures. Occasional cells with typical cytopathic nuclear changes and specific nuclear immunofluorescence were present in the seventh passage after transformation. The demonstration of the SV40 complement-fixing tumor antigen in the transformed cells confirmed the specificity of the transformation. Electron microscope evidence for the early intranuclear multiplication of the virus and preliminary observations of the ultrastructure of the transformed cells are presented.