In sodium pentobarbital-anesthetized dogs with spontaneous nasal blood flow or constant-flow vascular perfusion of the nasal mucosa, we measured nasal airway resistance, vascular resistance, and arterial inflow and outflow of the anterior and posterior venous systems. Acetylcholine in low doses (< 5 micrograms/kg per minute, intraarterially) increased nasal airway resistance, and the response was greater in dogs with spontaneous blood flow. Nasal vascular resistance was decreased. However, the posterior venous outflow was increased and the anterior venous outflow was decreased in dogs with constant-flow vascular perfusion. Acetylcholine in higher doses (> 5 micrograms/kg per minute, intraarterially) decreased nasal airway resistance, and vascular resistance fell further, but both venous outflows were increased in dogs with spontaneous blood flow or constant-flow vascular perfusion. The results indicate that acetylcholine may increase or decrease nasal airway resistance, depending on the dose administered, probably via a dose-dependent differential action on different components of the nasal vascular bed.