There is a high incidence of bacterial, viral, and fungal infections among long-term heroin users suggesting that the use of opioids alters resistance to infectious disease. Studies in my laboratory have shown that opioid treatment induces pronounced alterations of a number of in vivo immune responses in laboratory animals, including alterations of the induction of nitric oxide, a key molecule for host defense against bacterial infection. We also have discovered overwhelming evidence implicating a role of the central nervous system (CNS) in opioid-induced immune alterations. This discovery has led to our research investigating environmental and behavioral processes that influence opioid-immune interactions. The results of our investigations have demonstrated that alterations of immune status can be induced by the stimuli associated with the administration of opiates, indicating that the detrimental health consequences of opiate use may also be conditioned to the environmental stimuli and not solely the pharmacological property of the drug. Our current investigations are directed at determining the neural mechanisms involved in the conditioned and unconditioned effects of opioid on immune status.