Orthonasal or retronasal presentation of certain odours in everyday life, such as cheese or fish, evokes different responses. To study this phenomenon, stimulation techniques were developed to allow ortho- or retronasal presentation of chemosensory stimuli. Based on this technique, several studies were performed to investigate: (a) the subjects' ratings of stimulus intensity, hedonic characteristics of the stimuli, and stimulus quality; (b) the peripherally obtained electro-olfactogram; (c) EEG-derived olfactory event-related potentials; and (d) cerebral activation using functional magnetic resonance imaging; additional experiments investigated (e) the differential sensitivity of the nasal mucosa to trigeminal stimuli; and finally (f) clinical observations were obtained from patients with nasal polyposis with regard to ortho- or retronasal presentation of chemosensory stimuli. Summarizing these results, the studies indicate that there are perceptual differences in relation to ortho- and retronasal stimulus presentation. They appear to relate to: (i) contextual effects; (ii) subtle differences in nasal airflow, therefore access of stimuli to the olfactory epithelium may play a role in perceptual differences; in addition (iii) differential trigeminal sensitivities of the respiratory epithelium, possibly in combination with (iv) differential wiring of olfactory receptor neurons, may contribute to the observed differences in the perception of stimuli presented through the ortho- or retronasal routes.