The cardiovascular effects of locally applied nicotine and capsaicin to the nasal mucosa were studied in anaesthetized guinea-pigs. Local application of capsaicin (0.3-30 microM) or nicotine (0.3-30 mM) induced dose-dependent increases in arterial blood pressure, mainly due to an increase in peripheral vascular resistance. The capsaicin and nicotine responses were abolished after local anaesthesia and markedly reduced (to about 20% of control) by combined pretreatment with phentolamine and propranolol, suggesting reflexogenic sympathetic activation. Systemic capsaicin pretreatment abolished the hypertensive effect of capsaicin (30 microM) and reduced the response to nicotine application to about 25% of control (p less than 0.001). Local capsaicin pretreatment of the nasal mucosa one week earlier also significantly reduced the capsaicin response (p less than 0.05), while the nicotine-induced increase in blood pressure was not significantly changed. The present findings suggest the presence of two afferent mechanisms in the nasal mucosa which induce hypertension upon chemical irritation. The capsaicin response is dependent upon capsaicin-sensitive afferents. The nicotine response involves mainly capsaicin-sensitive neurons and, in addition, a minor component which is resistant to capsaicin pretreatment. Thus, the hypertensive effect of nicotine applied locally to the nasal mucosa seems to be mainly mediated via sensory mechanisms other than the sneezing response which is not dependent on capsaicin sensitive nerves.