Both Epstein-Barr virus (EBV) and p53 have independently been associated with idiopathic pulmonary fibrosis (IPF). This study explores further whether a relationship potentially exists between EBV and p53 in IPF, thereby providing a possible mechanism for the role of EBV in the disease progression of IPF. Lung tissue from open lung biopsies of 14 IPF patients was compared with a control group of 19 patients. EBV status was determined using both immunohistochemistry and PCR, while p53 expression was assessed with immunohistochemistry Seven of 14 IPF patients expressed p53 compared to one of 19 control subjects (P = 0.011). Eight IPF patients and no controls were positive for EBV (P < 0.01). Four IPF patients demonstrated both EBVand p53 expression compared with no controls, (P = 0.05). This study suggests that a relationship between EBV and p53 may exist in patients with IPF.