Polyelectrolyte complex (PEC) of chitosan (CH) and hyaluronic acid (HA) are widely used for skin, cartilage, and bone tissue engineering. However, no reports are seen on their response at high ionic media, like increased Ca2+ where they are likely to be exposed in the form of bone constructs and the influence of these ions on modulating the release of incorporated entities such as drugs and growth factors. Here, we prepared freeze dried scaffolds of PEC of CH and HA (CH-HA) and characterized them by FTIR, TGA, SEM, and ESEM. FITC conjugated BSA, designated as FA, was incorporated into the PEC to study the release properties in response to Ca2+. The swellability of CH-HA and the extent of drug release from the matrix, FA loaded CH-HA was studied in deionised water and aqueous Na+ and Ca2+ solutions. Swelling and drug release were high for the matrix in aqueous Ca2+ whereas it was remarkably low in water and Na+. Drug released was found to increase with concentrations of Ca2+ (0.02-1.0M) indicating that CH-HA is a promising matrix for Ca2+ responsive delivery of agents to accelerate healing of bone cracks, which is known to release high amount of Ca2+. POLYM. ENG. SCI., 55:2089-2097, 2015. (c) 2015 Society of Plastics Engineers