Antibody 38C2 catalyzed a retro-aldol process upon dendritic modified aliphatic polyesters. This catalytic system was studied in detail and displayed rate enhancements, k(cat)/k(uncat), of greater than 10(6). These antibody-catalyzed reactions took place in a stepwise manner yielding partially modified aldol-dendrimers until a fully substituted aldehyde dendrimer was formed. The catalytic antibody 38C2 only reacted with surface-exposed aldol moieties and did not significantly interact with the core groups for dendrons 4 and 8. For a higher generation dendron 8 the rate of unmasking slightly decreased presumably due to steric crowding of the aldol functionalities. In addition, catalytic antibody 38C2 was able to selectively differentiate block-hybrid dendrons and was regiospecific in the retro-aldol reaction of dendron 21. This is an inaugural report of a catalytic antibody utilizing dendrimers as substrates and suggests that antibodies could be used as selective catalysts for the controlled release and activation of specific molecules attached to biodegradable polymeric materials. Furthermore, this is the first example of catalytic antibody 38C2 displaying regioselectivity on a multifunctional aldol substrate. Important for synthetic applications is the antibody's ability to selectively differentiate regions on dendritic substrates and produce partly aldol functionalized dendrons under conditions mild enough to avoid beta-elimination.