Apoptin, a chicken anemia virus protein, was reported to induce tumor specific apoptosis, which was correlated with the nuclear localization of the protein in tumor cells. While in normal human cells, Apoptin was detected mainly in the cytoplasm and did not induce apoptosis. Using a recombinant adenovirus expressing Apoptin, we have found that Apoptin induced G(2)-M cell cycle arrest and chromatin condensation in cancer cells. Here we report that adenovirus mediated Apoptin expression also induces G(2)-M arrest in normal cells. In normal cells Apoptin is localized mainly in the cytoplasm but is also found in the nucleus of a subset of cells. Apoptin induces chromatin condensation not only when it is expressed in the nucleus but also when it is expressed in the cytoplasm. Our results indicate that Apoptin-induced chromatin condensation in the normal cells may not correlate with its nuclear localization and the mechanism of regulating the G(2)-M transition might be a target for Apoptin.