The use of ion-selective electrodes (ISEs) to study the binding of various organic ions to alpha- and beta-cyclodextrins (CDs) is described. The ISEs respond selectively, directly, and continuously to the activity of the free ion of interest in solution. Binding parameters (intrinsic binding constants and number of binding sites) are calculated with a computer program which performs a nonlinear fit of the Scatchard model to the experimental data (electrode potential versus total ion concentration) of a titration of a CD solution with the ion of interest. Electrodes selective to chloramine-T, naproxenate, p-nitrophenolate, and chlorpromazine ions were used as models. One binding site was found for all cases, with binding constants varying from 0.67 x 10(3) M-1 (naproxenate to beta CD) to 1.27 x 10(4) M-1 (chlorpromazine to beta CD) at 25 degrees C and a CD concentration of 0.010 M. Precision for the estimations of the binding parameters was 2.0-7.5% within run and 8-10% between run (n = 3). Nonspecific binding was observed for CAT: beta CD and CPM: beta CD interactions. The effects of pH, temperature, CD concentration, and ionic strength on the binding are also presented. The overall binding phenomenon is discussed in light of the estimates of the thermodynamic parameters in relation to the size of the guest molecule, the possible mechanism(s) involved, and the forces participating in the interaction of ions with CDs.