We are investigating the mechanism of catalysis in a class of molecules known as ribozymes. The main focus is on two self-cleaving RNA sequence found in a human pathogen, hepatitis delta virus (HDV). HDV is an unusual viral pathogen in that it is a satellite of hepatitis B virus and contains a small circular RNA genome. We are investigating both the structure and function of the self-cleaving ribozymes in the RNA; a key element in the replication of the virus that is responsible for processing replication products into viral size genomes. Initial work established the conditions required for cleavage and led us to propose a novel secondary structure for the HDV RNA sequence required for self-cleavage. This secondary structure correctly describes most, but not all, of the essential Watson-Crick interactions of the ribozyme and has revealed a key region of the RNA that may be involved in formation of the catalytic center. Currently, biochemical approaches are applied to the study of the role of metal ions and nucleobases in the mechanism of catalysis. In addition, we are interested in the process of folding and the importance of both alternative secondary structure and more subtle conformational changes to catalysis and regulation. Due to the small size and inherent stability of the HDV ribozymes, they have turned out to be excellent model systems for studying these questions.