Experimentally determined values of density (rho), speed of sound (u) and viscosity (eta) have been used to investigate solute-solvent interactions of L-histidine in aqueous ampicillin sodium (an antibacterial drug) solutions at different concentrations (0.035, 0.055, 0.075 and 0.095) mol kg(-1), over a wide range of temperatures (293.15, 298.15, 303.15, 308.15 and 313.15) K and at atmospheric pressure. The experimentally determined density (q) data has been used to obtain various parameters, for instance: apparent molar volume (VU), limiting apparent molar volume (V-Phi(o)), limiting apparent molar volume of transfer (V-Phi,tr(o)), limiting molar expansivity (E-Phi(o)) and hydration number (n(H)). The speed of sound (u) data helps to enumerate apparent molar isentropic compression (K-Phi,K-S), limiting molar isentropic compression (K-Phi,S(o)), limiting apparent molar isentropic compression of transfer (K-Phi,(S),(o)(tr)) and hydration number (n(H)) i.e., the number of water molecules hydrated to the amino acid. Relative viscosity (eta(r)), Jones-Dole coefficient-B (B) and viscosity B-coefficients of transfer (B-tr) were calculated from viscosity (eta) data. The results obtained from this data, showed the existence of physico-chemical interactions, (i.e., hydrophilic-ionic and hydrophilic-hydrophilic) in ampicillin sodium L-histidine solutions. The structure making behaviour of L-histidine in aqueous ampicillin sodium solution was studied in terms of Hepler's constant (partial derivative V-2(Phi)o/ partial derivative T-2)(P), coefficient of thermal expansion (alpha) and temperature derivative of B-coefficient (dB=dT). (C) 2017 Elsevier Ltd.