For crystals composed entirely of light atoms with atomic numbers close to each other, the Sayre equation gives the sign relation of the structure amplitudes. It has been successfully applied to the determination of crystal structures of organic compounds. Nevertheless, for crystals containing "heavy atoms", the Sayre equation is no longer valid; instead, the so-called "heavy atom method" is generally used. In the present work the interrelation between the respective signs of structure amplitudes, the Sayre equations, and heavy atoms has been considered, and the possibility of combining the heavy atom method and that of Sayre is pointed out. This leads to the suggestion of a sign-refinement procedure, with which the initial signs of heavy atoms can be refined to the correct signs of the structure amplitudes. This procedure has been verified with a hypothetical one-dimensional structure and proved to be efficient. Some problems concerning its application to the actual crystal-structure analysis are also discussed.