Gustatory stimuli, such as sugar, induce a behavioral response in Drosophila that involves extension of the proboscis and consumption of the sugar-containing solution. Addition of salt to the sugar solution inhibits this behavioral response. However, the mechanisms and gene products involved in the salt aversion response have not been described. Here, we report the identification of a locus, defective proboscis extension response (dpr), that is required for salt aversion. dpr was expressed in a subset of primary neurons in the gustatory organs and encoded a protein with two Ig-like domains, a single putative transmembrane domain, and a short region C terminal to the transmembrane segment. In addition, DPR defines a large previously unknown group of > or =20 highly related Ig-containing proteins.