To compare sensitivity of clinical methods (physical examination, electrocardiogram, and chest radiograph) to echocardiography in the detection of cor pulmonale, and to determine the role of nocturnal oxygen desaturation in its development, 33 non-hypoxemic patients who had severe chronic obstructive pulmonary disease (COPD) were evaluated by clinical methods, echocardiography, and overnight ear oximetry. Compared to 25 age-matched control subjects, COPD patients had higher peak pulmonary systolic pressures by contrast-enhanced Doppler (40 +/- 13 versus 22 +/- 5 mm Hg, or 5.3 +/- 1.7 versus 2.9 +/- 0.7 kPa) and ratios of right to left ventricular volume (1.1 +/- 0.6 versus 0.6 +/- 0.1, both p less than 0.05). Defining cor pulmonale as pulmonary hypertension, right ventricular enlargement, or right ventricular hypertrophy, 25 COPD patients (75 percent) had cor pulmonale by echocardiography and 13 (39 percent) by clinical methods (p less than 0.05). Nocturnal desaturation was present in only 21 percent of patients. Echocardiographic measurements were similar between patients with emphysema and patients with bronchitis, and between patients with and without sleep desaturation. In patients who have severe COPD without waking hypoxemia, cor pulmonale is detected nearly twice as often by echocardiography as by clinical methods, but is usually not associated with sleep desaturation.