Twenty persons living at an altitude of 2,240 meters were studied in order to examine the relative roles of passive and active factors in the genesis of pulmonary arterial hypertension in obesity (overweight, 75 +/- 39 percent). Pulmonary arterial hypertension was present in 80 percent (16) of the patients (mean pulmonary arterial systolic pressure, 45 +/- 17 mm Hg). In 95 percent (19) of the 20 patients, resistance to pulmonary flow at the end of diastole was increased (estimated mean pulmonary arteriolar resistance, 210 +/- 144 dynes.sec.cm-5; mean pulmonary arterial diastolic-pulmonary wedge pressure gradient 7.86 +/- 1.40 mm Hg). The mean arterial oxygen pressure was 50 +/- 9 mm Hg, the arterial carbon dioxide tension was 37 +/- 6 mm Hg and the arterial pH was 7.42 +/- 0.08. Since the pulmonary arterial systolic pressure has been reasonably predicted (r = 0.91; P < 0.001), it would appear that the compliance of the elastic pulmonary arteries in obese patients follows a normal pattern. The behavior of the right ventricular end-diastolic pressure at rest (mean change, 4.6 mm Hg; P < 0.001) and of the pulmonary wedge pressure (mean change, 4.7 mm Hg; P < 0.001) during passive lifting of the legs was indirect evidence of the increase in pulmonary blood volume. The presence of an abnormal resistance to pulmonary blood flow at the end of diastole is suggestive of a decrease in the distention of the pulmonary microcirculation. The pulmonary arterial diastolic-pulmonary wedge pressure gradient and the pulmonary arterial diastolic pressure were related to arterial oxygen unsaturation (r = 0.70; P < 0.05) but not to the concentration of hydrogen ions; thus hypercapnic acidemia appears as a secondary factor in the genesis of pulmonary arterial hypertension at high atitudes. The explanation could be the relative hyperventilation of high altitudes, with a compensatory metabolic alkalosis. The increased pulmonary blood volume and the alveolar hypoxia are the main causes in the pathogenesis of pulmonary arterial hypertension in the grossly obese patient at this altitude.