The effects of avian influenza virus (AIV) infection on systemic phagocytes and pulmonary macrophages of turkeys were studied. There was a significant increase (P < 0.0001) in oxidative burst in systemic phagocytes of AIV-inoculated turkeys on 2, 4, 6, and 8 days postinoculation (PI), as measured by chemiluminescence. There was also a significant increase (P < 0.02) in oxidative burst in pulmonary macrophages on day 4 PI. The chemiluminescence response was depressed on 6, 8, and 10 days PI in AIV-inoculated turkeys compared with controls. The increase in oxidative response in both systemic phagocytes and pulmonary macrophages correlated with the peak virus titer in the lungs and trachea of AIV-inoculated inoculated turkeys. Bacterial killing by pulmonary macrophages from AIV-inoculated turkeys was reduced on days 6 and 10 PI compared with uninoculated controls. Histopathological changes in trachea were more pronounced on day 6 PI in AIV-inoculated turkeys; no significant changes were detected in the lungs. These data indicate that compromised functional capacity of pulmonary macrophages predisposes turkeys to secondary bacterial infections.