We have previously reported a drop in wasted ventilation fraction (VD/VT) during exercise in patients with pulmonary vaso-occlusive diseases associated with collagen vascular disorders, despite an abnormally high mean pulmonary artery pressure and pulmonary vascular resistance at rest and during exercise. To further evaluate the diagnostic value of VD/VT measurements, we studied 8 subjects with normal spirometry, lung volumes and single-breath diffusing capacity who had previously demonstrated a high VD/VT at rest and during exercise. We found normal pulmonary hemodynamics in these subjects despite an abnormal rest and exercise VD/VT. Our findings effectively exclude hemodynamically significant pulmonary vascular obstruction, and do not support the use of VD/VT as a screening method for detecting diffuse pulmonary vaso-occlusive diseases.