The solubility and the acid base properties of risedronic acid (RA) were studied in NaCl and (C2H5)(4)NI aqueous solutions at different ionic strengths and at T = 298.15 +/- 0.1 K. The solubility of RA in the two salts is very different; in fact in NaCl(aq) the total solubility increases with increasing salt concentration up to m(NaCl) approximate to 2 mol.kg(1). For m(NaCl) > 2 mol.kg(1) the solubility slightly decreases, whereas an opposite trend is observed in (C2H5)(4)NI(aq). The solubility in water is 0.00274 mol.dm(3). From the analysis of the solubility measurements it was possible to determine the Setschenow and the activity coefficients of the neutral species. The four protonation constants of RA were then determined in similar experimental conditions and were analyzed in two ways, considering (i) the variation of the activity coefficients with ionic strength and (ii) the formation of weak complexes between the ions of the supporting electrolytes with the ligand species (a weak complexes model). In the first case, the DebyeHuckel and the specific ion interaction theory were used. The specific interaction and the activity coefficients of the various protonated species were also computed, for example epsilon (Na+,RIS4) = -0.211 +/- 0.008 and epsilon ((C2H5)(4)N+,RIS4) = 2.8 +/- 0.1. According to the weak complexes model, six species were determined, namely the NaRIS, NaHRIS, NaH2RIS, NaH3RIS, Na2RIS, and Na2HRIS (RIS = risedronate anion). The protonation sequence of RIS was studied computationally in aqueous environment with explicit water molecules. It was possible to evidence that two tautomers of H2RIS are formed at approximately 50:50 concentration ratio, and two protons are either placed on two phosphonate groups or distributed between a phosphonate group and a pyridine ring. This finding is important as the HRIS and H2RIS species are mainly present at the blood plasma pH of 7.4.