This project will examine the effect of morphine on parameters of immune function in normal macaques or macaques chronically infected with Simian Immunodeficiency Virus (SIV), the best model for human infection with HIV. Peripheral blood mononuclear cells collected before and after SIV infection oropioid treatment will be used to assess Natural Killer cell activity, responses to T and B cell mitogens, and levels of proinflammatory cytokines. The effect of the drug on immune status and SIV viral load will be made longitudinally in each animal, as well as among animals in a treatment group and between groups. One third of HIV infected individuals in the U.S. are intravenous drug abusers. Morphine is the primary active metabolite of heroin, and is the classic opioid used in most laboratory studies. Morphine is known to be immunosuppressive in animal models and has been shown to up-regulate HIV replication in vitro. Yet, the effect of opioid drugs on progression of retroviral infections in vivo has never been definitively established, nor has the effect of opioids on parameters of immune function been evaluated in retrovirally infected animals. Natural Killer cell activity, mitogen responses, and cytokine profiles are the standard functional tests that have been used in the majority of published studies examining effects of opioids on immune status, and therefore have been chosen for this project. The proposed studies will provide new data on the effects of chronic treatment with morphine on immune status in uninfected macaques, as well as testing the effects of chronic morphine in SIV infected animals, on immune status and disease progression, including neurological involvement. A novel aspect of the proposed studies is that the effect of morphine will be tested on SIV infection when the drug is given before or after the virus. Also, few studies in any species have examined the effects of chronic opioid treatment on immune functional parameters. The data collected in the proposed work will be novel, and will help to answer the questions directly as to whether opioids affect progression of a retroviral infection in primates, and whether the drug alters functional immune responses.