AbstractWe hypothesize that gaseous ammonia (NH3) released into respiratory airways can neutralize inhaled acidic particles and alter or mitigate their toxicity. To test this hypothesis, we have examined the relationship between respiratory NH3and the chemical neutralization of inhaled sulfuric acid (H2SO4) aerosol in the surgically isolated upper airways of anesthetized dogs.With air entering via the mouth, the NH3concentration measured at the larynx, ranged between 30 and 225 parts per billion (ppb). The extent of neutralization at this point ranged from 8%‐70% (n = 16) for the 0.5‐μm particles and 7%‐22% (n = 6) for the 1.0‐μm particles. With air entering via the nose, the laryngeal NH3concentration ranged between 50 and 220 ppb. Neutralization values were between 15%‐65% (n = 8) for 0.5‐μm particles, and between 16%‐18% (n = 3) for 1.0‐μm particles. For both routes of entry, the extent of neutralization was correlated with the laryngeal NH3concentration. We conclude that the chemistry of acidic particles is significantly altered by respiratory NH3during inhalation. The extent of neutralization is related to both the NH3concentration in the airway and the size of the particle entering the airway. The extent of neutralization per ppb of laryngeal NH3is related to the route of entry, being greater for the