Background: Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disorder characterized by episodic deposition of heterotopic bone in place of soft connective tissue. All FOP-associated mutations map to the BMP type I receptor, ALK2, with the ALK2R206H mutant form found in the vast majority of patients. The mechanism(s) regulating the expressivity of hyperactive ALK2R206H signaling throughout a patient's life is not well understood. Results: In Drosophila, human ALK2R206H receptor induces hyperactive BMP signaling. As in vertebrates, elevated signaling associated with ALK2R206H in Drosophila is ligand-independent. We found that a key determinant for ALK2R206H hyperactivity is a functional type II receptor. Furthermore, our results indicate that like its Drosophila ortholog, Saxophone (Sax), wild-type ALK2 can antagonize, as well as promote, BMP signaling. Conclusions: The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2R206H receptors. Our studies provide a compelling example for Drosophila as a model organism to study the molecular underpinnings of complex human syndromes such as FOP. Developmental Dynamics 241:200–214, 2012. © 2011 Wiley Periodicals, Inc.