Thirty-eight mutants of RNase Sa (ribonuclease from Streptomyces aureofaciens) were examined for their structure, thermal sensitivity, and tendency to aggregate. Although a biphasic correlation was seen between the effect of temperature on structure and the free energy of transfer changes in many of the mutants, little correlation was seen between the time at which aggregation is initiated or the rate of aggregation and the thermal sensitivity of the mutants. It is hypothesized that the nature of contacts between protein molecules in the associated (aggregated) phase rather than structural changes dominates the aggregation process for these series of mutants.