Most odorants, in addition to the olfactory system, also activate the intranasal trigeminal system. Recent studies have shown that pure trigeminal stimulation activates somatosensory regions as well as regions traditionally thought of as primary olfactory areas. As a main aim of this study we wished to a) ascertain which brain regions are responsive to an "artificially" bimodal odor composed of a trigeminal (CO2) and an olfactory stimulant (phenyl ethyl alcohol, PEA) and b) determine if presenting CO2 and PEA simultaneously activates different brain regions than when presenting them individually. Fifteen men were scanned using functional magnetic resonance imaging while smelling PEA, CO2, and a mixture of both Stimuli (CO(2)PEA) presented simultaneously. Odors were presented monorhinally to the right nostril in a block design. The contrast between CO(2)PEA and baseline revealed areas implicated in the processing of both olfactory and trigeminal stimuli. When the mixture was contrasted with the sum of its single components (CO(2)PEA-{CO2+PEA}), activations in integration centers (left superior temporal and right intraparietal sulcus) and in orbitofrontal areas (left medial and lateral orbitofrontal cortex) were detected. The opposite contrast ({CO2+PEA}-CO(2)PEA) did not reveal any significant activation. In contrast to studies which have used natural mixed olfactory/trigerninal stimuli, we have shown that the perception of an artificial mixed olfactory/trigerninal stimulus activates, as opposed to inhibiting the olfactory cortex. Further, we also conclude that a mixed olfactory/ trigeminal stimulus appears to lead to higher cortical activations than the sum of its parts. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.