The thermal denaturation of iron-free and iron human serotransferrin has been studied by differential scanning calorimetry. At pH 7.9 in 0.05M Tris, 0.1M NaHCO3 buffer, two transitions (Td = 60.1 degrees, 70.7 degrees C), at a 5 degrees C/min heating rate, were observed for iron-free serotransferrin. The respective enthalpies of denaturation were found to be 143 and 229 kcal/mol. Iron serotransferrin exhibits a single thermogram peak with Td = 83.4 degrees C and delta H = 616 +/- 15 kcal/mol (linearly extrapolated to 0 degrees C/min heating rate), at pH 7.8. An activation energy of 104 kcal/mol was computed by the procedure of Beech. A value of 112 kcal/mol was calculated from a first-order kinetics Arrhenius plot. Rate constants were determined at several temperatures from the onset temperature to Td. Denaturation temperatures and enthalpies were linearly dependent on heating rates. The thermal denaturations of iron-free and iron serotransferrins are irreversible, under the experimental conditions used. In contrast to conalbumin, thermograms of serotransferrin solutions partially saturated with ferric ions exhibit only the peaks corresponding to those obtained on separate DSC scans of iron-free and iron serotransferrin, respectively.