DNA intramolecular hairpins are appropriate models for the thermodynamic description of the pseudo-intramolecular melting behavior of native DNA. To improve our understanding of the stability and melting behavior of DNA secondary structures and of the physical properties of nucleic acids, we have carried out a thermodynamic investigation of all possible bulges and mismatches in the hairpin molecule: d(GCNGCT5GCGC) and d(GCNGCT5GCMGC), where N represents a bulged base and N-M represents a W-C or mismatched base pair. We used circular dichroism spectroscopy to determine the overall conformation of each hairpin and UV melting and differential scanning calorimetry techniques to characterize their unfolding thermodynamics. The majority of hairpins melted in two-state monophasic transitions with transition temperatures independent of strand concentration. Relative to the host hairpin with 4 dG-dC base pairs in the stem, all hairpins with a bulge or a mismatch are less stable, while the hair-pins with an extra canonical base pair are more stable. In both cases, the effects arc enthalpy driven, indicating a loss or gain in base-pair stacking interactions, respectively. We also obtained linear enthalpy-entropy compensations with slopes (or compensating temperatures) of 317 K (hairpins with lesions) and 395 K (hairpins with fully paired stems) which are indicative of processes that are driven by solute-solvent interactions. These compensating temperatures are in excellent agreement with the results of similar analysis of data sets of other laboratories. Therefore, the relative change in enthalpy contribution for a given hairpin is partially compensated by a change in their overall hydration. These results suggest that the inclusion of bulges and mismatches immobilizes additional structural water while the addition of a W-C base pair immobilizes electrostricted water.