The invention provides polypeptides containing .alpha.-MSH that can be used to treat diseases characterized by inflammation and/or autoimmunity. Also included in the invention are .alpha.-MSH analogs and nucleic acids encoding polypeptides containing .alpha.-MSH and .alpha.-MSH analogs optionally linked to heterologous sequences. Also included in the invention are methods of delivering .alpha.-MSH containing peptides, .alpha.-MSH analogs, an DNA encoding .alpha.-MSH and .alpha.-MSH analogs.