Hox proteins potentially regulate many targets within individual developing tissues, but how they selectively regulate diverse target genes and activate or repress target gene expression is poorly understood. To address these questions, Walsh and Carroll investigated the repression of the spalt(sal) gene by the Hox protein Ubx in the developing Drosophila hindwing (haltere) (see p. 3585). Using both genetic and biochemical approaches, they found that two Smad proteins (Mad and Med), which are required for sal activation in the wing, collaborate with Ubx to directly repress sal in the haltere. This repression occurs via a sal cis-regulatory element that contains closely spaced Smad and Ubx binding sites and is perfectly conserved among four Drosophila species. Because Smad and Ubx proteins appear not to interact directly, the authors argue that they might instead `collaborate' to co-regulate sal, and that collaboration might be a widespread requirement for Hox function in which two or more regulatory proteins bind to the same site but not to each other.