Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) is used as a pulmonary function test (PFT) to assess gas transfer in the lungs. The implications of a low DLCO are well-recognized, but the clinical significance of a high DLCO is not clear. The aim of this study was to identify the clinical correlates of a high DLCO.We identified 245 patients with a high DLCO (ie, > 140% predicted) and a matched group of 245 patients with normal DLCO (ie, 85 to 115% predicted), who were selected from a laboratory database of 45,000 patients tested between January 1997 and December 1999. We compared the demographic features, clinical diagnoses, and PFT data between the two groups.Large multispecialty group practice.The patients in the high DLCO group were heavier (mean [+/- SD] weight, 96.0 +/- 22.9 vs 85.0 +/- 21.3 kg, respectively; p < 0.001), had a higher mean body mass index (32.9 +/- 7.4 vs 29.4 +/- 6.4 kg/m(2), respectively; p < 0.001), larger body surface area (p < 0.001), and larger mean total lung capacity (p = 0.007) and alveolar volume (p < 0.001). The clinical diagnoses of obesity (p < 0.001) and asthma (p < 0.001) were more common among patients with high DLCO values. The majority of patients (62%) with a high DLCO had a diagnosis of obesity, asthma, or both. Polycythemia, hemoptysis, and left-to-right shunt were uncommon.A high DLCO on a PFT is most frequently associated with large lung volumes, obesity, and asthma. Other conditions are much less common. A clinical condition, which typically reduces DLCO, may deceptively normalize DLCO in such patients.