GENERAL acid-base catalysis contributes substantially to the efficacy of many enzymes, enabling an impressive array of eliminations, isomerizations, racemizations, hydrolyses and carbon-carbon bond-forming reactions to be carried out with high rates and selectivities(1). The fundamental challenge of exploiting similar effects in designed catalysts such as catalytic antibodies(2,3) is that of correctly positioning the catalytic groups in an appropriate active-site microenvironment, Charge complementarity between antibody and hapten (the template used to induce an antibody) has been used successfully in a number of instances to elicit acids and bases within immunoglobulin combining sites(4-9), but the activities of the catalysts obtained by this strategy are generally considerably lower than those of natural enzymes, Here we report that by optimizing hapten design and efficiently screening the immune response, antibodies can be obtained that act effectively as general base catalysts. Thus a cationic hapten correctly mimicking the transition-state geometry of all reacting bonds and bearing little resemblance to the reaction product has yielded carboxylate-containing antibodies that catalyse an E2 elimination with more than 10(3) turnovers per active site and rate accelerations of greater than 10(8). These results demonstrate that very large effects can be achieved by strategic use of haptenic charge.