Abstract Thermal properties of bovine brain fodrin have been studied by circular dichroism and electron spin resonance and compared to those of bovine erythrocyte spectrin. Protein unfolding was induced either by urea or by a combination of heat and urea. The denaturation profiles of the two proteins, as measured by the changes in ellipticity at 222 nm as a function of temperature, were very similar but fodrin denaturation occurred at both higher temperatures and higher urea concentrations. In the absence of urea the thermal transition of spectrin was centered at 51 °C and that of fodrin at 54.5 °C. Proteins were also labeled with a maleimide analog spin probe. Spin-labeled fodrin showed a thermal transition similar to that of spectrin but centered at 46 °C instead of 42 °C. These findings indicated a close structural similarity of the two proteins but a slightly higher conformational stability of fodrin to both heat and urea.