To identify the determinants of survival in patients with idiopathic pulmonary fibrosis (IPF), we performed a survival analysis on 74 subjects with IPF. The study subjects were on average 64 yr of age (range, 25 to 83 yr), 62% were male, and 29% were never smokers. A tissue diagnosis was made in 67 (91%) of our study subjects. These subjects were followed for a mean period of 4 yr (range, 1.4 to 118.8 months) after the onset of pulmonary symptoms. During the period of observation, 41 subjects died (median survival = 28.2 months) and 33 continue to survive (median follow-up period = 60.9 months). A univariate analysis demonstrated that diminished survival was significantly associated with male gender (hazard ratio = 1.98; 95% confidence interval [CI] = 1.01-3.85), a higher FEV1/FVC ratio (hazard ratio = 1.82 [per 10% increase in the FEV1/FVC ratio]; 95% CI = 1.21-2.73), a lower percent predicted FVC (hazard ratio = 0.74; 95% CI = 0.60-0.91), a lower percent predicted total lung capacity (TLC) (hazard ratio = 0.75; 95% CI = 0.60-0.94), a lower percent predicted diffusing capacity of carbon monoxide (DLCO) (hazard ratio = 0.69; 95% CI = 0.53-0.89), a higher ILO profusion category on chest radiograph (hazard ratio = 3.52; 95% CI = 1.58-7.87), and an enhanced release of prostaglandin E2 (PGE2) by cultured alveolar macrophages (hazard ratio = 1.32 [per 10 pm/ml of PGE2]; 95% CI = 1.07-1.62).(ABSTRACT TRUNCATED AT 250 WORDS)