This project was designed to titrate the influence of pyridostigmine injected intraarterially on pulmonary resistance and gas exchange in pigs and dogs. Pyridostigmine at 1 mg/kg reduced red blood cell cholinesterase activity 28-35% that was not significantly reduced further with doses up to 9 mg/kg. Plasma cholinesterase was reduced by 80% in the dog and 40% in the pig with 1 mg/kg of pyridostigmine and with 3 mg/kg it was reduced to 40% in the pig and 10% in the dog. Higher doses had no further significant effect. Breathing resistance (cm H2O/l/s) in the pig was doubled as a linear function with 9 mg/kg pyridostigmine. In the dog, breathing resistance went to a maximum of 8 cm H2O/l/s from a control value of 1 cm H2O/l/s with 3 mg/kg of pyridostigmine but did not go higher with doses up to 9 mg/kg. PaO2 was reduced by approximately 20% in the pig and 15% in the dog with pyridostigmine doses of 6-9 mg/kg. These experiments indicate that significant alterations in pulmonary function do not occur until acute dosages in the range of 3-6 mg/kg are reached. Furthermore, acute administration of large doses of pyridostigmine results in salivation and gastrointestinal stimulation well in advance of any impairment of respiratory function.