We here report that after infection with human herpesvirus 6A, human cord blood mononuclear cells accumulate in G(2)/M phase of the cell cycle. Experiments with foscarnet or ultraviolet (UV)-irradiated virus stocks pointed at an (immediate-)early, newly formed viral protein to be responsible for the arrest. At the molecular level, p53, cyclin B(1), cyclin A and tyrosine(15)-phosphorylated cdk1 accumulated after HHV-6A infection, indicating an arrest in G(2). However, no change was observed in the levels of downstream effectors of p53 in establishing a G(2) arrest, i.e. p21 and 14-3-3sigma. We thus conclude that the HHV-6A-induced G(2) arrest occurs independently of p53 accumulation.