Preventing apoptosis during the early stages of infection of a host cell is generally thought to result in a higher yield of progeny virus. The US3 protein kinase of pseudorabies virus (PRV) and herpes simplex virus (HSV) is able to protect infected cells from apoptosis, which may be one of the reasons why both US3null PRV and US3null HSV replicate to lower virus titres in several cell types. However, such potential correlation between the higher amount of apoptosis in US3null virus-infected cells and the lower virus titres of US3null virus has not been investigated directly. In the current study, we found that a broad-spectrum caspase-inhibitor efficiently inhibited apoptosis in swine testicle and human laryngeal epidermoid carcinoma cells infected with US3null or wildtype (WT) PRV. However, inhibition of apoptosis did not affect US3null or WT PRV extracellular or cell-associated virus titres, nor did it restore the small plaque phenotype of US3null PRV