The paper describes methods which allow intranasal irritation using short- and long-lasting painful stimuli in humans. Short-lasting pain is induced by gaseous CO2, while long-lasting pain is induced by a stream of dry air. Both models have been explored regarding their major determinants, e.g. stimulus duration, stimulus intensity, or repeated stimulation. Short-lasting, non-inflammatory pain stimuli seem to provide specific indicators of A(delta)-fiber function, while responses to long-lasting, inflammatory pain appear to be indicative of C-fiber function. Responses to both types of painful stimuli are modulated by analgesic drugs. As these well-investigated models allow the detailed and precise analysis of modulatory effects on intranasal nociception, they appear to be suited for the investigation of subtle changes of intranasal irritation, e.g. induced by environmental agents. (C) 2002 Elsevier Science B.V. All rights reserved.