Opioid peptides found in the general circulation can modulate several functions of phagocytic cells that are related to their microbicidal and cytotoxic activity. Since reactive oxygen species are crucial to these activities, the affect of opioid peptides on superoxide (O-2) generation was evaluated with the use of lucigenin-enhanced chemiluminesence (CL). beta-Endorphin and dynorphin stimulate the production of O-2 in human polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PMO) at peptide concentrations that prevail systemically (10(-14)-10(-12)M). There is an inverse dose-response relation for PMN but not PMO. The effect is rapid and sustained in PMN (peak CL at 2-4 min, duration greater than 15 min), whereas it is rapid but brief in PMO (peak 1 min, duration less than 3 min). Naloxone inhibits CL responses by greater than 75% in both cell types.