The aim of this project was to develop an early reading intervention for children with Down syndrome based on the related behavioral phenotype. The intervention targeted learning of letter–sound correspondences, reading of decodable and high frequency words, and phonological awareness. We evaluated the feasibility and potential efficacy of the intervention with seven children between the ages of 6 and 8 years who participated in a series of multiple-probe across lessons single-case design studies. Results indicate a functional relation between the intervention and mastery of taught content for three students. Two students demonstrated positive although inconsistent response; two students demonstrated limited learning. Implications for future research and practice are discussed.