The effects of moderate sustained normocapnic hypoxia on tracheal submucosal gland reflex responses were studied. Experiments were performed in anesthetized, paralyzed, and mechanically ventilated dogs. The changes in the number of secreting glands and volume of secreted fluid in the subsequent period of time were recorded after 15-30 min of controlled ventilation with room air [arterial PO2 (PaO2) 86 +/- 3 Torr], hypoxic gas mixture (PaO2 49 +/- 4 Torr), or 100% O2 (PaO2 339 +/- 39 Torr), under isocapnic and isohydric conditions. The hillocks method was used to quantify the changes in submucosal gland secretion. The changes in secretion 30 s after stimulation of pulmonary C-fiber receptors by right atrial injection of capsaicin (10 micrograms/kg; n = 10) were markedly lower during moderate hypoxia than in normoxia or hyperoxia. Differences in the number of liquid droplets and the volume of secreted fluid were statistically significant (P < 0.05 and P < 0.001, respectively). Stimulation of airway rapidly adapting receptors by lung deflation increased airway secretion; the number of "hillocks" and the volume of secreted fluid were lower in hypoxic than in hyperoxic state. Differences between response curves for the number of glands activated and secreted volume were statistically significant (P < 0.05 and P < 0.001). The number of glands activated by substance P given locally by arterial infusion was not affected by the state of oxygenation, but the calculated volume of secreted fluid was lower during the hypoxic state than under hyperoxic condition (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)