In polymyositis/dermatomyositis (PM/DM), a rapidly progressive interstitial pneumonitis (RPIP) which is a fatal complication of unknown etiology has received increasing attention. We have encountered 9 RPIP cases among 150 PM/DM cases in the past 10 years. To investigate the pathogenic role of viruses in RPIP, we examined lung specimens from patients with RPIP in PM/DM for the presence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) using polymerase chain reaction (PCR) and in situ hybridization (ISH). We analyzed 21 specimens from RPIP in PM/DM (n = 9), collagen diseases (n = 6; 4 had interstitial lung disease), and controls (n = 6). EBV was frequently detected in RPIP (7/9 by PCR 3/9 by ISH), but was also detected in other collagen diseases of the lungs. In lung specimens from both patients with RPIP in PM/DM and those with collagen diseases, EBV was significantly detected (13/15 by PCR, 5/15 by ISH, P < 0.005) compared to controls (1/6 by PCR, 0/6 by ISH). CMV was detected by ISH in 2 RPIP patients but in none of he others, though by PCR CMV was detected equally in the three groups studied. These findings indicate that a direct involvement of EBV or CMV in RPIP of PM/DM is unlikely, although it is possible that an immune response to latent viruses or viral products in PM/DM may have a role in the pathogenesis of the RPIP.