CD23/FceRII, the low-affinity receptor for IgE, is a multifunctional protein of importance in blood cell development and the immune system. We have studied the interaction of CD23 with IgE in solution using hydrodynamic methods applied to recombinant fragments of both ligands: sCD23, corresponding to the soluble lectin domain of CD23, and Fce3−4, a dimer of the Ce3−Ce4 sequence of IgE. The hydrodynamic, spectroscopic, and biological properties of these fragments suggest that they have a fully native structure. Sedimentation equilibrium studies on mixtures of sCD23 and Fce3−4 indicate that IgE has two binding sites for CD23, each characterized by affinities of approximately 105 M-1. Analysis of the sedimentation as a function of temperature allows conclusions to be drawn about the thermodynamics of binding at the two sites. Binding at the first site is characterized by large changes in enthalpy (ΔH°To = −2.1 ± 3.3 kcal mol-1) and heat capacity (ΔCp° = −320 ± 320 cal mol-1 K-1), whereas binding at the seco...