A dual-variable domain-immunoglobulin (DVD-Ig) is an engineered protein that combines the function and specificity of two monoclonal antibodies in one molecular entity. A DVD-Ig is designed as an IgG-like molecule, except that each light chain and heavy chain contains two variable domains in tandem through a short peptide linkage, instead of one variable domain in IgG. The fusion orientation of the two variable domains and the choice of linker sequence are critical to functional activity and efficient expression of the molecule. A DVD-Ig can be produced by conventional mammalian expression systems as a single species for easy manufacturing and purification. A DVD-Ig has the specificity of the parental antibodies, is highly stable in vivo, and exhibits excellent IgG-like physicochemical and pharmacokinetic properties. The design and development of a DVD-Ig are described.