AbstractCopolymers ofL‐lysine andL‐isoleucine [poly(L‐Lysf,L‐Val1 −f)] containing 4–15% isoleucine were investigated using potentiometric titration and circular dichroism (CD) spectroscopy. With increasing isoleucine content, β‐sheet formation is favored over α‐helix formation at high pH and room temperature. The fraction of β‐sheet present, as a function of pH, calculated from titrations of poly(L‐Lys85.2,L‐Ile14.8), agreed well with data obtained from CD studies for the same copolymer. Thermodynamic parameters were determined from titrations using the method of Zimm and Rice; the partial free energy (ΔG°C → β) at 25° for the coil‐to‐β‐sheet transition for isoleucine was estimated to be −515 cal/mol; from the temperature dependence of free energy, the partial entropy (ΔS°cβ), and the partial free enthalpy (ΔH°c → β) of the coil → β transition for isoleucine is estimated to be 2.6 e.u. and 260 cal/mol, respectively. The partial thermodynamic parameters obtained for lysine are in good agreement with literature values. It is concluded from these studies that isoleucine