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Despite its use since 1944, the mechanism of DEET repellency remains controversial. Here, we revisited the role of smell and taste in DEET repellence using <jats:italic>Drosophila<\/jats:italic> as a model.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Analysis of the responses of individual olfactory receptor neuron (ORN) classes to DEET reveals that 11 ORNs are activated and two are inhibited by this compound. Blocking individual ORN classes in the antenna does not block DEET repellence. This argues against the existence of a single ORN mediating DEET repellence in <jats:italic>Drosophila<\/jats:italic>. Activation of all ORCO\u2010expressing neurons using channelrhodopsin favors attraction, not repellence, in behavioral valence. We also demonstrate that gustatory neurons are highly sensitive to DEET. We used RNA interference to screen candidate receptors encoded by gene families involved in the detection of bitter compounds, including 34 gustatory receptors (<jats:italic>Grs<\/jats:italic>), 14 ionotropic receptors (<jats:italic>Irs<\/jats:italic>), five pick\u2010pocket subunits (<jats:italic>PPKs<\/jats:italic>), three transient receptor potential ion channels (<jats:italic>TrpA<\/jats:italic>, <jats:italic>TrpL<\/jats:italic>, <jats:italic>Painless<\/jats:italic>) and one metabotropic glutamate receptors gene (<jats:italic>DmXR<\/jats:italic>). We saw striking defects in DEET\u2010mediated oviposition behavior when expression of either <jats:italic>Gr32a<\/jats:italic> or <jats:italic>Gr33a<\/jats:italic> was inhibited.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Our findings support a multimodal mechanism for DEET detection in fruit flies and indicate a prominent role for taste detection mediating DEET repellence. \u00a9 2019 Society of Chemical Industry<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.5592","type":"journal-article","created":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T04:39:51Z","timestamp":1566275991000},"page":"880-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Multiple channels of DEET repellency in 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