It is widely known that ions in the aqueous phase affect the binding of charged solutes to membranes. Here we report the effect of ions and urea on the interaction of both the charged and uncharged forms of the local anesthetic tetracaine (TTC, an aminoester derivative of benzoic acid) to zwitterionic micelles. Binding was monitored by the increase in TTC fluorescence. Shifts in the emission wavelength maximum (Lax) indicated that the anesthetic was located in an environment of lower polarity. The neutral form of TTC bound to micelles to a larger extent than the protonated form, in agreement with results found for lipid bilayers (Boulanger, Leitch, Schreier and Smith, Can. J. Biochem. 58, 986-995, 1980). When ions from the Hofmeister series and urea were compared in their ability to affect the partitioning of the anesthetic, binding of both the charged and uncharged forms was found to increase upon addition of S042and CI-but was seen to decrease in the presence of SCN-, C104-and urea. Solubility measurements revealed that the solubility of uncharged TTC increases in solutions containing the additives in the following order: S042-< C1-< C10,-< dilute buffer < SCN-< urea. Spin label EPR spectra indicated that, except for C104-, the ions had little effect on micellar structure. Static light scattering measurements corroborated this result indicating a large increase in micellar molecular weight in the presence of C104-and lesser increases for C1.-and SCN-. The results show that, besides affecting the binding of ionic species through an electrostatic mechanism, ions also act by altering water structure and, as a consequence, the water solubility and the tendency to partition into the less polar micellar environment of polar charged or uncharged small organic solutes such as the benzoic acid ester derivative. Moreover, evidence suggests that the ions bind directly to the zwitterionic polar groups of the micelles, leading to changes in structure and size.