Opioid treatment has been shown to cause generalized immunosuppression leading to an increased incidence of opportunistic disease and infection. Although it is well established that opioids, such as morphine, cause profound dysregulation of immune cell function, the role of alterations in gene expression in this response have not been reported. Identifying the intracellular pathways in immune cells involved in opioid-mediated immunosuppression is important for understanding the mechanisms responsible for increased disease susceptibility in HIV infection and addiction. To test the hypothesis that the immunosuppressive effects of morphine are mediated via dysregulation of genes in circulating leukocytes, the experiments proposed here will use a microarray to profile changes in gene expression and these results will be further verified using Taqman real-time PCR and western blotting. The specific aims of this proposal are to: 1) utilize a microarray gene expression profiling strategy to identify dysregulated genes within circulating blood leukocytes as potential mediators of morphine induced immunosuppression, 2) verify changes in gene expression using Taqman real-time PCR, 3) demonstrate changes in protein levels of dysregulated genes, 4) determine whether the dysregulation in genes is centrally or peripherally mediated.