The plant hormone auxin is central in many aspects of plant development. Previous studies have implicated the ubiquitin-ligase SCFTIR1 and the AUX/IAA proteins in auxin response. Dominant mutations in several AUX/IAA genes confer pleiotropic auxin-related phenotypes, whereas recessive mutations affecting the function of SCFTIR1 decrease auxin response. Here we show that SCFTIR1 is required for AUX/IAA degradation. We demonstrate that SCFTIR1 interacts with AXR2/IAA7 and AXR3/IAA17, and that domain II of these proteins is necessary and sufficient for this interaction. Further, auxin stimulates binding of SCFTIR1 to the AUX/IAA proteins, and their degradation. Because domain II is conserved in nearly all AUX/IAA proteins in Arabidopsis, we propose that auxin promotes the degradation of this large family of transcriptional regulators, leading to diverse downstream effects.