In this study we have used isothermal titration calorimetry, ITC, and circular dichroism spectropolarimetry, CD, to directly measure the thermodynamics and the structural changes for binding histones, H11 and H14, to DNA. The ITC data have been used to estimate the binding constant, (K ≈ 108) and the enthalpy change (ΔH ≈ + 5 (H11 at 25ºC), ΔH ≈ +20 kcal/mol (H14 at 15 ºC) for formation of the H1/DNA complex. CD data indicate that both H1 and DNA are partially unfolded in the H1/DNA complex. Protein and DNA unfolding must contribute to the large unfavorable endothermic enthalpy change for complex formation. The ITC data indicate that the H11 binding site is comprised 30 DNA base pairs while H14 interacts with approximately 36 DNA base pairs. At saturation, our data are consistent with 100% of the H1 binding sites being occupied in the H1/DNA complex.