The aspartate receptors of Escherichia coli and Salmonella typhimurium which mediate chemotactic responsiveness to aspartate have 79% amino acid sequence identity but exhibited apparently quite different aspartate binding plots. The Scatchard plot of the Salmonella receptor was concave upward whereas the E. coli receptor gave a straight line. Because the two binding sites in the Salmonella receptor lacking aspartate have a 2-fold crystallographic symmetry axis and do not overlap, the observation of more than one class of binding sites must be due to a ligand-induced conformational change giving negative cooperativity. The closely related E. coli receptor was found to bind with only one class of sites but with a stoichiometry of one aspartate per dimer. The E. coli receptor thus binds with half-of-sites reactivity, an extreme form of negative cooperativity in which the second ligand is not observed to bind at all. Comparison of the X-ray crystal structure of the ligand binding domain with and without bound aspartate revealed ligand-induced conformational changes that explain the two examples of negative cooperativity.