The nature of facial pain in rhinosinusitis does not always correspond to the severity of an inflammatory process. The inflammatory response of the nasal and paranasal sinus mucosa may be enhanced by neurogenic inflammatory mediators. Objective: to study the role of the neurotransmitter substance P in the pathogenesis of pain symptoms in rhinosinusitis. Subjects and methods. A total of 380 patients with rhinosinusitis with varying magnitude of pain syndrome were examined using a multidimensional verbal-color painful test. Serum substance P levels were determined by an enzyme immunoassay. All the patients underwent a complete clinical and laboratory examination. A control group consisted of healthy young people aged 20—32 years without chronic diseases. Results. In the presence of an adequate pain symptom characteristic of nasal and paranasal sinus diseases, the serum concentration of substance P is not greater than 2000 pg/ml. In this case, the pain symptom corresponds to the severity of the inflammatory process, and nasal and/or paranasal sinus diseases require conventional therapy for inflammatory diseases of the upper respiratory tract. Very high serum substance P concentrations of more than 2000 pg/ml appear as a pronounced pain symptom, reflect the involvement of neurogenic mechanisms in the inflammatory process and require pathogenetic therapy.