The aim of this work was to gain an insight into the self-associative processes and drug solubilization ability of a Tetronic variety, T904 (4 x 15 EO units; 4 x 17 PO units; HLB 15), in aqueous media covering the physiological range of pH and ionic strength, applying isoperibol microcalorimetry, transmission electronic microscopy (TEM), dynamic light scattering (DLS), oscillatory rheometry, and drug diffusion experiments. T904 shows two pK(a) (pK(a1)=4.0 and pK(a2)=7.9) and, at pH<5.8, the diprotonated form predominates over the non-protonated one. Deprotonization of the central diamine group is a required condition for micellization, which is an endothermic entropy-driven process owing to hydrophobic interactions between the PPO chains. As the pH of the solutions decreases, the coulombic repulsions among the positively charged amine groups make the aggregation more difficult, raising the critical micellar concentration (CMC) and decreasing the size of the micelles. The changes in the conformation and hydrophilicity of the Tetronic were reflected in its gelation temperature (around 30 degrees C at neutral-alkaline pH; no gelation at pH<2) and solubilization capacity for griseofulvin (2-fold greater at neutral-alkaline pH than at pH<2) and rate of diffusion (slower at pH 7.4). Such alterations in self-assembly are relevant when using Tetronic in the design of drug delivery systems.