Schizophrenia and bipolar disorder are serious neuropsychiatric diseases with a high morbidity and social cost. We hypothesize that these and other serious neuropsychiatric disorders may represent the result of environmental insults occurring in susceptible individuals. Our laboratory is exploring the possible role of viruses and other microbial agents as environmental factors in schizophrenia in bipolar disorders. These studies are performed by application of genomic techniques such as subtraction libraries, differential display, reverse transcription polymerase chain reaction and serial analysis of gene expression (SAGE): These studies have generally been performed using brain tissue from individuals with schizophrenia, bipolar disorder and other psychiatric diseases from the Stanley Neuropathology Network. Studies performed up to this point in time indicate that the brain of individuals with schizophrenia and bipolar express RNA species in a pattern different from that of individuals with other psychiatric diseases and from unaffected controls. Identifiable RNA species which are differentially expressed in the brains of individuals with serious psychiatric diseases include those encoding neurotransmitter transport proteins, transcriptional activators, immune response proteins and endogenous retroviruses. The RNA's encoding endogenous retroviruses are of particular interest since they may represent the interactions between infectious virions and human genetic elements. In addition, the brains of individuals with schizophrenia and bipolar disorders express novel RNA's which do not display significant levels of homology with known human genes. Several of these RNA's display homology of genes of other vertebrate and invertebrate species while others do not display homology with any known nucleic acids. These novel RNA's may represent undiscovered human genes, new infectious agents, or combinations both genetic and microbial nucleic acids. Our work supports the role for both genetic and environmental factors in the etiopathogenesis of human psychiatric disorders