Although the in vitro immunomodulatory effects of morphine are well-documented, few studies have explored the impact of morphine on viral infection in intact rats. We report that morphine can alter in vivo immune responsiveness to pulmonary influenza virus infection in Lewis rats. We studied rat-adapted influenza virus (RAIV) infection, which is a unique infectious disease system because normal rats develop an acute inflammatory response to RAIV in the lung, and rapidly clear the virus within a few days, with no mortality (13,20,21). Male Lewis rats were implanted with 75 mg morphine pellets or placebo pellets 72 hours prior to intranasal RAIV infection. Rats were euthanized at 2, 24, 48, 72 and 96 hours after infection and inflammation and viral load were measured in the lungs. Placebo-treated rats showed marked inflammatory responses to RAIV infection, and quickly cleared the virus from their lungs. Morphine-treated rats mounted less vigorous inflammatory responses to the infection and cleared the virus more slowly than placebo-treated rats. Although these initial data indicate that morphine can alter the response to RAIV, additional studies are necessary to fully characterize these effects.