The thermal denaturation of ribonuclease A and lysozyme in aqueous solutions of osmoregulatory solutes methylamines [trimethylamine N-oxide, betaine (trimethylammonioacetate) and sarcosine] and urea have been investigated by differential scanning calorimetry (DSC). The transition temperature, heat capacity and enthalpy of denaturation in aqueous solutions of ribonuclease A and lysozyme at pH 6.00 have been determined by a least-squares fit of the excess heat capacity data to the two-state model. Thermodynamic functions of denaturation, ΔG°, ΔH° and ΔS° at various temperatures have also been evaluated. The methylamines increase the thermal stability of ribonuclease A and lysozyme in the order : trimethylamine N-oxide > sarcosine > betaine. The stabilizing effect of methylamines when compared with that of amino acids follows the order : trimethylamine N-oxide > glycine > β-alanine > γ-aminobutyric acid > sarcosine > serine > α-alanine > betaine > proline. The structure-stabilizing effect of methylamines and structure-destabilizing effect of urea on ribonuclease A are nearly additive. No net effect on the stability of ribonuclease A is observed in a 2 : 1 mixture of urea and methylamines.