The effect of incremental exercise to exhaustion on the change in pulmonary clearance rate (k) of aerosolized (99m)Tc-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) and the relationship between k and arterial PO(2) (Pa(O(2))) during heavy work were investigated. Ten male cyclists (age = 25 +/- 2 yr, height = 180.9 +/- 4.0 cm, mass = 80.1 +/- 9.5 kg, maximal O(2) uptake = 5. 25 +/- 0.35 l/min, mean +/- SD) completed a pulmonary clearance test shortly (39 +/- 8 min) after a maximal O(2) uptake test. Resting pulmonary clearance was completed >/=24 h before or after the exercise test. Arterial blood was sampled at rest and at 1-min intervals during exercise. Minimum Pa(O(2)) values and maximum alveolar-arterial PO(2) difference ranged from 73 to 92 Torr and from 30 to 55 Torr, respectively. No significant difference between resting k and postexercise k for the total lung (0.55 +/- 0.20 vs. 0. 57 +/- 0.17 %/min, P > 0.05) was observed. Pearson product-moment correlation indicated no significant linear relationship between change in k for the total lung and minimum Pa(O(2)) (r = -0.26, P > 0.05). These results indicate that, averaged over subjects, pulmonary clearance of (99m)Tc-DTPA after incremental maximal exercise to exhaustion in highly trained male cyclists is unchanged, although the sampling time may have eliminated a transient effect. Lack of a linear relationship between k and minimum Pa(O(2)) during exercise suggests that exercise-induced hypoxemia occurs despite maintenance of alveolar epithelial integrity.