First-pass lung uptake of propranolol was studied in 10 patients with normal lungs, 8 patients with severe pulmonary emphysema, and 1 patient with primary pulmonary hypertension. Propranolol uptake was measured by comparing the ratio of [14C]propranolol (0.5 mg) to indocyanine green (5 mg) injected into the right atrium with the ratio of their concentrations in arterial blood collected over the duration of the first-pass dye outflow curve. Mean uptake was 69 +/- 4% (n = 18) in patients with normal lungs; 55 +/- 7% (n = 13) in patients with emphysema (p less than 0.001), and 51% in the patient with primary pulmonary hypertension. Cardiac index in the normal group (2.78 +/- 0.48 L/min/M2, n = 16) was not significantly different from the group with emphysema (2.90 +/- 0.48, n = 12). There was no correlation between lung uptake and conventional lung function indexes in patients with emphysema. We conclude that propranolol uptake is reduced when the pulmonary vascular bed is damaged. This may have pharmacologic consequences, and it is possible that other pharmacokinetic functions of the lung may similarly be impaired in pulmonary disease. The method is relatively simple, and may be suitable for assessing pulmonary endothelial function in patients with lung disease.