Abstract A method for the in vivo quantification of transpulmonary shunting in man is described. This method is safe and can be simply performed at the time of a lung scan. To measure shunting, the radioactivity arriving in a systemic capillary bed (in the head) after an intravenous dose of technetium-99m-labeled albumin microspheres is compared to the activity arriving in the same capillary bed after an intravenous dose of unbound activity. The assumptions necessary for this comparison were tested in dogs with surgically created transpulmonary shunts. Shunting was quantified in 75 subjects, 10 normal men and 65 patients with a variety of diseases, including pulmonary embolism and chronic obstructive lung disease. No shunting greater than 3.5 per cent was observed in 71 of the 75 studies. In one patient, a transient shunt of sixteen per cent was found. The 3 other patients had congenital cyanotic heart disease, and significant shunting was shown in each. It is concluded that anatomic transpulmonary shunts are not an important feature of the lung diseases studied and that associated hypoxemia is probably due to underventilation or diffusion abnormalities of perfused areas of lung.