The synthesis and characterization of water-soluble random copolymers containing L-histidine with JVs-(4-hydroxybutyl)-L-glutamine, and the thermally induced helix-coil transitions of these copolymers in water and in aqueous 0.5 N KC1 solution, are described. The incorporation of both charged and uncharged L-histidine was found to decrease the helix content of the polymer in water, even in the presence of 0.5 N KC1, which effectively shields the electrostatic repulsions among charged L-histidine residues in the a-helical and coil conformations. The Zimm-Bragg parameters and s for the thermally induced helix-coil transition of charged and uncharged poly(L-histidine) in water and in 0.5 N KC1 were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. At physiological temperature, 37 °C, the helix-coil stability constants, s, for charged and uncharged L-histidine are similar, viz., 0.66 and 0.70, respectively. This demonstrates that ionization-deionization of histidine residues does not in itself affect the conformational stabilities of proteins. The synthesis of AZ-acetyl-N-methylhistidinamide and its titration, as well as that of the copolymers, in 0.1 N KC1 are described. Finally, the values of and s, determined for 18 amino acids from experiments on host-guest random copolymers, and those obtained for cystine and proline by extrapolation, are summarized here.