Odors we perceived in our environment are mainly the result of mixtures of odorants. The first step of odor perception is an interaction between these odorant mixtures and olfactory receptors. The corresponding transduced olfactory signals, conveyed by olfactory sensory neurons, are then processed by the brain (Zou et al. 2006). In previous studies, we investigated the perception of a mixture including specific proportions of ethyl isobutyrate (strawberry-like odor) and ethylmaltol (caramel-like odor). This specific mixture was especially judged as more typical of a pineapple odor than the individual components (Coureaud et al. 2008, Le Berre et al. 2008, Coureaud et al. 2009). Assuming that combinations of activated ORs encode odor qualities and that molecules sharing a same odorant quality possess common structural molecular property (Furudono et al. 2009, Saito et al. 2009), our assumption was that molecule sharing strawberry, caramel or pineapple odor should also share several common structural characteristics. To test this hypothesis, we used Common Feature Pharmacophore Generation protocol (Catalyst HipHop) implemented in Discovery Studio 2.1 (Accelrys Inc.) to generate a pharmacophore hypothesis in the absence of known receptor(s). The Catalyst/ HipHop program (Clement et al. 2000) is a powerful tool that explores the conformational space and derives a pharmacophore based on features that are common to active molecules. In our study, the pharmacophoric features considered are hydrogen bond acceptors (HBA) and surface of accessible hydrophobic regions (HY). We selected 19 molecules in the Flavor Base 2004 (Leffingwell and Assoc.): 7 molecules described as ‘‘strawberry’’, 6 molecules as ‘‘caramel’’ and 6 molecules as ‘‘pineapple’’. We then performed HipHop Pharmacophore Generation on each subset separately. Two HY and two HBA constitute the best pharmacophore models obtained for ‘‘strawberry’’ and for ‘‘pineapple’’ subsets, whereas the best ‘‘caramel’’ pharmacophore is constituted by one HY and three HBA. A pharmacophore comparison leads to obtain a good mapping of these three pharmacophore models, putting forward a common spatial arrangement of chemical features. This result suggests that the molecules sharing strawberry, caramel or pineapple odor probably recognize a common OR set. An identification of target ORs would be the next step to understand the early biochemical mechanism supporting blending odor mixture perception. O.O. Clement and A. Mehl, in Pharmacophore perception, Development and Use in Drug Design, O. F. Gu¨ner (Eds.), La Jolla, 2000, pp. 69-84; G. Coureaud, T. Thomas-Danguin et al. Physiol. Behav. 95 (2008) 194-199; G. Coureaud, Y. Hamdani et al. J. Exp. Biol. 212 (2009) 2525-2531; Y. Furudono, Y. Sone et al. Chem. Senses 34 (2009) 151-158; E. Le Berre, N. Beno et al. Chem. Senses 33 (2008) 389-395; H. Saito, Q. Chi et al. Sci. Signal. 2 (2009) 1- 14; Z.H. Zou and L.B. Buck Science 311 (2006) 1477-1481.