The present invention relates a modified human interferon beta (INF.beta.) which is less immunogenic than human INF.beta. (SEQ ID NO: 1) when administered in vivo to a human. The modified human INF.beta. comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.