In experiments lasting 311 +/- 8 (SE) min, we studied the clearance of 125I-fibrinogen ([125I])RIF) from distal lung units of anesthetized, ventilated dogs. We instilled varying concentrations of isosmolar, citrated [125I]RIF ranging from 0.75 to 4 mg/ml into alveoli of individual dogs, and we monitored clearance by the use of external detectors and blood and lymph sampling. Approximately 9% [125I]RIF passed into proximal airways according to detector signal analysis. Excluding airway flow, whole lung clearance of [125I]RIF occurred by degradation to small molecules that rapidly became evenly distributed in body extracellular water. The degradation appeared to take place within the distal airway and not within the lung interstitium because 131I-fibrinogen, injected intravenously, was degraded less in passing from plasma to right duct lymph. The intra-alveolar kinetics of [125I]RIF had 1.5 reaction order with a specific rate of 1.27 X 10(-5) ml(3/2)-mg(-1/2)-min(-1). The data indicate that fibrinogen clearance from alveoli occurs by both transbronchial bulk flow and intraalveolar degradation.