H. influenzae is an important childhood pathogen. Approximately 10,000 children each year acquire menigitis due to this organism; of these, most survive but over 50% have permanent neurological damage. As a consequence, H. influenzae is one of the leading causes of postnatally acquired mental retardation. Ninety-five percent of invasive H. influenzae disease is due to type b organisms. Therefore, the type b capsule is thought to be an important virulence factor. To better understand the pathogenesis and prepare a vaccine suitable for use in children under the age of two, we intend to clone the capsule genes. A physiologic animal model which mimics the human disease will be used as a virulence assay. The cloned capsule genes will also be used as a molecular probe to define the genetic relationship of unencapsulated H. influenzae to type b organisms. Understanding the genetic basis of invasive H. influenzae disease, and the regulation of capsulation of type b organisms will allow us to develop a vaccine which will be useful in very young children and eliminate H. influenzae infection. Neurological damage and mental retardation would then be prevented.