We report the development of new bioactive coatings of biomaterials based on the alternate deposition of oppositely charged polyelectrolytes. We selected polylysine (PLL) and poly(glutamic acid) (PGA) for the polyelectrolytes and murine melanoma cells as a biological test model system. These cells respond specifically to a small peptide hormone, alpha-melanocortin, which is a potent stimulator of melanogenesis. We show that a synthetic alpha-melanocortin derivative, covalently coupled to PLL forming the outer layer of a multilayer film remains as biologically active as the free hormone. Furthermore, the long time activity of the hormone is maintained when embedded in multilayer architectures whereas its short time activity depends on integration depth. The embedding of bioactive molecules not only anchors them irreversibly on the biomaterial, but opens also the possibility to control their activity. In comparison to conventional coating methods, polyelectrolyte multilayers are easy to prepare and retain their biological activity after storage as dry material. These very flexible systems allow broad medical applications for implant and tissue engineering.