The effects of pH, temperature, and guanidinium chloride on the conformation of ribosomal protein L7/L12 have been investigated in order to understand the stability of this protein dimer. The results indicate that many of the molecular forces stabilizing the conformation of the dimer are disrupted at low pH or high temperature. These acid- and thermal-denatured states, however, still retain considerable secondary structure. Approximately half of the alpha-helical content present in the native protein remains intact at pH below 2 and at temperatures above 90 degrees C. Further denaturation of the acid-denatured protein by 6 M guanidinium chloride results in a state which still contains approximately 20% alpha helix. Similar amounts of residual conformation remain when the native L7/L12 dimer is denatured with guanidinium chloride. Thermodynamic analysis of the conformational transitions studied indicates that none is compatible with a simple two-state process. The complexity of these denaturation data and the structural characterizations of the various denatured states are consistent with the possible existence of structural domains in the protein molecule possessing different conformational stabilities.