Herpes simplex virus (HSV) is reported to produce marked cytopathogenic effect (CPE) in different cell cultures at least 1-3 days after infection. No stereological data for the CPE of any virus in cultured cells is available in the literature. In this study stereological methods were applied for the first time to estimate cell and nucleus volume of the infected Vero cell line with herpes simplex virus type 1 (HSV-1). Vero cells infected with HSV-1 were studied at 4, 9 and 25 h post-infection and compared to uninfected control cells using stereological methods. As compared with the uninfected control, the mean nucleus and cell volume of the HSV infected cells, increased approximately 53 and approximately 46%, respectively, 4 h post-infection. The methodology can be used to rapidly diagnose CPE changes of the viral infection of cell cultures especially for those viruses which do not produce obvious CPE at early stages. In addition, it is possible to explain the intensity of cytopathic changes like ballooning of infected cells or their nuclei. It means the methods can help us to understand how larger or smaller are the cells (or the nuclei) in comparison with the other groups and statistically analyse these changes at early stages.