The basic notions of transition state theory have been exploited in the past to generate highly selective catalysts from the vast library of antibody molecules in the immune system. These same ideas were used to isolate an RNA molecule, from a large library of RNAs, that catalyzes the isomerization of a bridged biphenyl. The RNA-catalyzed reaction displays Michaelis-Menten kinetics with a catalytic rate constant (k(cat)) of 2.8 x 10(-5) per minute and a Michaelis constant (K-m) of 542 mu M; the reaction is competitively inhibited by the planar transition state analog with an inhibition constant (K-i) value of similar to 7 mu M. This approach may provide a general strategy for expanding the scope of RNA catalysis beyond those reactions in which the substrates are nucleic acids or nucleic acid derivatives.