Halothane decreases alveolar fluid clearance (AFC), a function required for efficient gas exchange in the rat. Further, halothane decreases amiloride-sensitive Na+ transport in rat alveolar type II cells, a process responsible for a significant portion of AFC. We tested the hypothesis that halothane would decrease amiloride-sensitive AFC in rabbits. Rabbits anesthetized with 1.8% halothane had 5% albumin in 0.9% NaCl instilled into the right lung with (n = 11) or without (n = 11) 1 mM amiloride present in the instillate. Similarly, animals anesthetized with IV fentanyl and droperidol were administered 5% albumin solution with (n = 11) or without (n = 11) amiloride. At 90 min after instillation, alveolar fluid samples were obtained, and AFC was determined by changes in fluid protein concentration. Rabbits anesthetized with halothane or fentanyl and droperidol in the absence of amiloride had similar AFC values (35% ± 12% and 35% ± 7%, respectively, mean ± SD). Rabbits anesthetized with halothane or fentanyl and droperidol in the presence of amiloride had similar AFC values (20% ± 10% and 16% ± 12%, respectively) that were significantly less than the groups not administered amiloride (P < 0.01). Unlike the rat, the ability of the rabbit to dear fluid from the alveolar space through amiloride-sensitive pathways is not decreased by halothane anesthesia.