Proteins are transported via the cell membrane and can catalyze reactions, and many proteins form aggregates and amyloidal structures in conditions when they pass to intermediate states. Herein we have tried to clarify which amino acid residues determine the stability of the molten globule state of apomyoglobin. On the one hand, it can be proposed that the formation of this intermediate state is affected by hydrophobic amino acid residues in the protein hydrophobic core since it is known that at the first stage of folding hydrophobic collapse of the polypeptide chain occurs. On the other hand, we can suggest that the hydrophobic amino acid residues on the protein surface interacting with the solvent molecules also affect the molten globule state. The substitution of hydrophobic residues on the protein surface can have an effect on protein misfolding, i.e. decrease or increase the probability of formation of irregular hydrophobic contacts during protein folding. We have also postulated that the introduced disulfide bond can influence the molten globule state because the SS-bond should affect the mobility and compactness of the protein. By our hypothesis, the disulfide bond should be introduced on the protein surface so that the packing of the hydrophobic core of apomyoglobin would remain undamaged. To verify the above proposals, we have studied four mutant forms of apomyoglobin with substitutions of hydrophobic amino acid residues on its surface and ten mutant forms of apomyoglobin with substitutions of amino acid residues in the hydrophobic core of this protein. In addition, we have analyzed the mutant form of apomyoglobin with the introduced disulfide bond on the protein surface. They are large hydrophobic amino acid residues located in different structural elements of apomyoglobin. Earlier we investigated the effect of these residues on the rates of refolding and unfolding of the apomyoglobin structure. In this study, we analyze only the influence of single substitutions of hydrophobic amino acid residues on the stability of the molten globule state of apomyoglobin. Hydrophobic amino acid residues on the protein surface were also chosen for substitutions. Based on the crystal structure of myoglobin we selected residues that are maximally exposed to the aqueous environment and weakly interact with other amino acid residues of the protein. Six hydrophobic amino acid residues were selected to be substituted by hydrophilic ones. Four mutant proteins were examined: with substitutions of two, three, four and six amino acid residues. Later the mutant proteins were designated as m2, m3, m4, and m6, respectively. Fig. 1 shows a three-dimensional model of apomyoglobin. As can be seen, the chosen amino acid residues on the surface of apomyoglobin are grouped on one side of the protein. We suggest that such positions of residues can enhance the effect of mutation on the molten globule state of apomyoglobin.