The use of self-complementary structures in replication experiments is discussed, and a second generation of self-replicating molecules is introduced. Key design elements of the new system are described, specifically a high affinity (K-a similar to 10(5) M(-1) in CDCl3) between the two complementary reactive components and the careful placement of nucleophilic and electrophilic centers within the system. These considerations preclude intramolecular reactions within two-component complexes, thus minimizing undesirable background reactions. Autocatalysis is observed in the new systems, and by using appropriate control experiments the autocatalysis is traced to template effects.