Hepatitis C virus (HCV) is a new virus discovered in 1989. Since HCV is known to cause fibrotic changes in the liver, we studied whether HCV is involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Firstly, we assessed anti-HCV antibodies by enzyme-linked immunosorbent assay (ELISA) in the sera obtained from 66 IPF patients (46 males and 20 females; mean age +/- SEM, 61.5 +/- 10.1). We observed a significantly high prevalence of anti-HCV antibodies in IPF compared with 9,464 age-matched controls (28.8% vs 3.66%, p < 0.05). To confirm the results, recombinant immunoblotting assay (RIBA) was conducted on the 19 ELISA-positive sera, and 8 sera (12.2%) were found to be definitely positive. Secondly, we searched for HCV in the blood of IPF patients by reverse transcription-polymerase chain reaction. As preliminary data, four out of 28 cases (14.3%), all of which were pathologically diagnosed as UIP, were positive for HCV. In conclusion, although further investigation is required, a high prevalence of anti-HCV antibodies and the existence of HCV itself in the blood may suggest the possibility that HCV infection plays an important role in the pathogenesis of IPF.