This report describes the first direct comparison between the reactive immunization and transition state analogue hapten manifolds for catalytic antibody production. In an initial communication (Janda et al J. Am. Chem. Sec. 1997, 119, 10251) we described the use of a phosphonate diester hapten 5, in a reactive immunization approach, that elicited a panel of proficient biocatalysts for the hydrolysis of S-(+)-naproxen p-methylsulfonylphenyl ester (3b) [k(cat)(3b)/k(uncat)(3b) = 0.05-6.60 x 10(5)]. However, only moderate enantioselectivity was obtained when the panel of antibody catalysts was studied in a kinetic resolution of rac-3a, the best result leading to S-(+)-4a in 90% ee for 35% conversion of rac-3a. This report details a transition state analogue hapten approach to elicit antibody catalysts for this same process by employment of phosphonate monoester 6. This strategy has yielded a library of catalysts with excellent turnover numbers [k(cat)(3b)/k(uncat)(3b) = 0.14-19.0 x 10(5)] and enantioselectivities. Three of these catalysts, 6G6, 12C8, and 12D9, perform a useful kinetic resolution of rac-3a, generating S-(+)-naproxen 4a in >98% ee with up to 50% conversion. Comparing the two hapten strategies reveals that the antibodies, although elicited for the same reaction with the same substrate, exhibit quite different catalytic behavior. The transition state analogue approach has furnished better catalysts, in terms of turnover numbers and enantiomeric discrimination, but which possess varying degrees of product inhibition by phenol 9. Thermodynamic evaluation reveals that their catalytic power is derived almost entirely as a function of differential stabilization of the transition state over the ground state: K-m(3b)/K-i(8). By contrast, the reactive immunization approach has elicited more proficient biocatalysts that couple an efficient "catalytic" mechanism and improved substrate recognition with no product inhibition.