Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-gamma) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-gamma-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-gamma 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-gamma-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.