This study determined the effects of neuropeptides and neuroendocrine hormones at the cellular level of the immune response using a murine macrophage cell line, J774, which exhibits a chemiluminescent oxidative burst upon acute stimulation with zymosan. We report that the zymosan-triggered oxidative burst of J774 cells can be modulated by the opioid peptides beta-endorphin (beta-END) and dynorphin A (DYN) in a naloxone-reversible fashion. Norepinephrine (NE) also modulated chemiluminescence (CL) emission of J774 cells, with dose-dependent suppression of CL dependent upon co-incubation with gamma-interferon (gamma-INF). Without gamma-INF co-incubation, NE shared with the opioid peptides beta-END and DYN the ability to modulate oxidative burst, producing an inverted-U dose response. These data indicate that J774 cells may be useful for explaining some mechanisms through which the neuroendocrine system interacts with the immune system.