To achieve full ripening, climacteric fruits, such as tomato require synthesis, perception and signal transduction of the plant hormone ethylene. The nonripening phenotype of the dominant Green-ripe (Gr) and Never-ripe 2 (Nr-2) mutants of tomato is the result of reduced ethylene responsiveness in fruit tissues. In addition, a subset of ethylene responses associated with floral senescence, abscission, and root elongation are also impacted in mutant plants, but to a lesser extent. Using positional cloning, we have identified an identical 334-bp deletion in a gene of unknown biochemical function at the Gr/Nr-2 locus. Consistent with a dominant gain of function mutation, this deletion causes ectopic expression of Gr/Nr-2, which in turn leads to ripening inhibition. A CaMV35::GR transgene recreates the Gr/Nr-2 mutant phenotype but does not lead to a global reduction in ethylene responsiveness, suggesting tissue-specific modulation of ethylene responses in tomato. Gr/Nr-2 encodes an evolutionary conserved protein of unknown biochemical function that we associate here with ethylene signaling. Because Gr/Nr-2 has no sequence homology with the previously described Nr (Never-ripe) ethylene receptor of tomato we now refer to this gene only as GR. Identification of GR expands the current repertoire of ethylene signaling components in plants and provides a tool for further elucidation of ethylene response mechanisms and for controlling ethylene signal specificity in crop plants.