Retinal cell fate determination in Drosophila is controlled by an interactive network of genes, including eyeless, eyes absent, sine oculis and dachshund. We have investigated the role of the TGF-beta homolog decapentaplegic in this pathway. We demonstrate that, during eye development, while eyeless transcription does not depend on decapentaplegic activity, the expression of eyes absent, sine oculis and dachshund are greatly reduced in a decapentaplegic mutant background. We also show that decapentaplegic signaling acts synergistically with and at multiple levels of the retinal determination network to induce eyes absent, sine oculis and dachshund expression and ectopic eye formation. These results suggest a mechanism by which a general patterning signal such as Decapentaplegic cooperates reiteratively with tissue-specific factors to determine distinct cell fates during development.