Folding thermodynamics of nine heterodimeric, parallel coiled coils were studied by isothermal titration calorimetry (ITC) and thermal unfolding circular dichroism measurements. The heterodimers were composed of an acidic and a basic 30-residue peptide, which when in isolation were monomeric and essentially unstructured. The reaction followed a two-state mechanism indicating that folding and association were coupled. delta Hfold, delta Sfold and delta Cp normalized per mol of residue were of the same magnitude as for monomeric globular proteins, hence the energetics of folding and association of the heterodimeric coiled coils was balanced similarly to the folding of a single polypeptide chain. Cavity creating Leu/Ala substitutions revealed strong and position-dependent energetic coupling between leucine residues in the hydrophobic core of the coiled coil. delta Gunfold (equivalent to -delta Gfold in the two-state reaction) was determined from thermal unfolding. Global stability curves were calculated according to the Gibbs-Helmholtz equation and using the combined free energy data from ITC and thermal unfolding. Maximum stabilities were between 15 and 37 degrees C and cold denaturation could be demonstrated by direct calorimetry. The stability curves were based on free energies of folding measured between 10 and 85 degrees C and under identical solvent conditions. This represents a novel experimental approach which circumvents the use of varying solvent conditions as is typically required to measure protein stability curves. Discrepancies were noticed between van't Hoff enthalpies deduced from thermal unfolding and measured by direct calorimetry. The discrepancies are thought to be due to residual ordered structure in the denatured single chains around room temperature but not near the transition midpoint temperature Tm. This demonstrates that over an extended temperature range the assumption of a common denatured state implicit in the van't Hoff analysis may not always be valid.