Alginate hydrogels are used extensively in cell encapsulation, cell transplantation, and tissue engineering applications. Alginates possess many favorable properties required in biomaterials, but are unable to specifically interact with mammalian cells. We have therefore covalently modified alginate polysaccharides with RGD-containing cell adhesion ligands utilizing aqueous carbodiimide chemistry. The chemistry has been optimized and quantified with reaction efficiencies reaching 80% or greater. The concentration of peptide available for reaction was then varied to create hydrogels with a range of ligand densities. Mouse skeletal myoblasts were cultured on alginate hydrogel surfaces coupled with GRGDY peptides to illustrate achievement of cellular interaction with the otherwise non-adhesive hydrogel substrate. Myoblasts adhere to GRGDY-modified alginate surfaces, proliferate, fuse into multinucleated myofibrils, and express heavy-chain myosin which is a differentiation marker for skeletal muscle. Myoblast adhesion and spreading on these GRGDY-modified hydrogels was inhibited with soluble ligand added to the seeding medium, illustrating the specificity of adhesion to these materials. Alginate may prove to be an ideal material with which to confer specific cellular interactive properties, potentially allowing for the control of long-term gene expression of cells within these matrices.