We have demonstrated that 50µm diameter arteriovenous pathways exist in isolated, healthy human and baboon lungs ventilated and perfused under physiologic pressures. These findings have been confirmed and extended by demonstrating the passage of 25 µm microspheres through the lungs of exercising dogs, but not at rest. Determination of blood flow through these large diameter intrapulmonary arteriovenous pathways would be an important first step to establish a physiological role for these vessels. Currently, we sought to estimate blood flow through these arteriovenous pathways using Technetium-99m labeled macroaggregated albumin (^99mTcMAA) in healthy humans at rest and during maximal treadmill exercise. We hypothesized that the percentage of ^99mTcMAA able to traverse the pulmonary circulation (% transpulmonary passage) would increase during exercise. Seven male subjects without intracardiac shunts were injected with ^99mTcMAA at rest on one day and during maximal treadmill exercise on a separate day (>6days). Within 5 min after injection, subjects began whole body imaging in the supine position. Six of the seven subjects showed an increase in transpulmonary passage of MAA with maximal exercise. Using two separate analysis methods, % transpulmonary passage significantly increased with exercise from baseline to absolute values of 1.2 ± 0.8% (P=0.008) and 1.3 ± 1.0% (P=0.016), respectively (mean ±SD (paired t-test)). We conclude that MAA may be traversing the pulmonary circulation via large diameter intrapulmonary arteriovenous conduits in healthy humans during exercise. Recruitment of these pathways may divert blood flow away from pulmonary capillaries during exercise and compromise the lung's function as a biological filter.