Single breath pulmonary diffusing capacity for carbon monoxide (DL(CO)) was examined as a predictor of all-cause mortality among 4,333 subjects who were aged 25-74 years at baseline in the First National Health and Nutrition Examination Survey (NHANES I) conducted from 1971 to 1975. The relation of the percentage of predicted DL(CO) to all-cause mortality was examined in a Cox proportional hazard model that included age, sex, race, current smoking status, systolic blood pressure, serum cholesterol, alcohol consumption, body mass index, percentage of predicted forced vital capacity (FVC), and the ratio of forced expiratory volume at 1 second (FEV1) to FVC. Mortality had a linear association with the percentage of predicted FVC (rate ratio (RR) = 1.12, 95% confidence interval (CI) 1.08-1.17, for a 10% decrement) and a significantly nonlinear association with the percentage of predicted DL(CO) with an adverse effect that was clearly evident for levels below 85% of those predicted (RR = 1.24, 95% CI 1.12-1.37 for a 10% decrement). The relative hazard for the percentage of predicted DL(CO) below 85% was not modified by sex, smoking status, or exclusion of subjects with clinical respiratory disease on the initial examination. This association with the percentage of predicted DL(CO) was present among 3,005 subjects with FEV1 levels above 90% of those predicted. Thus, pulmonary diffusing capacity below 85% of predicted levels is a significant predictor of the all-cause mortality rate within the general US population independent of standard spirometry measures and even in the absence of apparent clinical respiratory disease.