One of the great aspirations of gene therapy is to eventually develop technology which will provide a feasible approach to correcting genetic defects and combating infectious diseases. The laboratory is engaged in studying the molecular biology of the defective human parvovirus adeno-associated virus (AAV) in hopes of developing a safe, efficient viral vector for human gene therapy. Ongoing research is revealing that this nonpathogenic human virus is now accessible for utilization as a vector. We have developed a packaging system which allows for efficient encapsidation of foreign genes into AAV virions. We have also identified the essential cis-acting sequencing required for efficient integration into host cell DNA. Finally, we have characterized this integration step and uncovered the exciting result of site-specific integration. this last observation clearly sets AAV apart as a eucaryotic viral vector and its potential for gene therapy in humans. Our continued efforts to understand and manipulate this virus as a vector has required a multi-faceted approach from basic virology in vivo to in vitro virus replication, integration, and packaging.