SUMMARY Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology, associated with DNA damage and malignancy. Bronchogenic carcinoma is the cause of death in 10 to 13% of IPF patients. Microsatellite Instability (MSI) and Loss of Heterozygosity (LOH) are frequently detected in cancers. If the above genetic alterations could be observed in IPF, they would possibly explain the higher relative risk of lung cancer. We investigated the incidence of MSI and LOH in sputum cytological specimens of 26 IPF patients and 26 healthy, matched subjects, using 10 highly polymorphic, microsatellite markers. The electrophoretic pattern of each specimen was compared with that of corresponding peripheral blood. Thirteen (50%) patients showed genetic alterations, either MSI or LOH. Five (19%) patients exhibited MSI and 10 (39%) LOH in at least one microsatellite marker. Three (12%) patients showed LOH in more than one marker. None of the healthy subjects exhibited genetic alterations in the studied markers. No correlation was found between the detected genetic alterations and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that the studied genetic alterations are frequent in IPF, seem not to be related with the severity of the disease, and may be related to tumorigenesis. Pneumon 2000, 13 (3): 187-195