Physiologic and pathologic responses of dogs were studied to assess the effect on the lungs of aspiration of gastric contents at a pH value greater than 2.5. Experimental solutions were administered into the lungs at a dose of 2 ml/kg. Animals were divided into 5 groups: group 1 (n = 13) received saline at a pH of 5.9; group 2 (n = 8) received hydrochloric acid (HCl) at a pH of 1.8; group 3 (n = 6) received gastric contents containing small food particles at a pH of 5.9; group 4 (n = 6) received gastric contents containing food particles at a pH of 1.8; group 5 (n = 6) received gastric contents at a pH of 5.9 from which food particles had been filtered. Arterial blood gas tension, fractional intrapulmonary shunt, and blood pressure were measured at intervals for 48 h. Animals that received gastric contents at a pH of 5.9 and severe hypoxia and increased intrapulmonary shunting that were significantly greater than those of animals receiving saline and were as severe as those of animals receiving HCl at a pH of 1.8. If food particles were in the aspirate, hypercapnia and acidosis were noted. There was pneumonitis in lung sections taken from animals in groups 2, 3, and 4, but not groups 1 and 5. These findings contradict the common belief that aspiration of gastric contents at a pH greater than 2.5 is benign.