Effects of Met-enkephalin (Met-ENK) and opioid antagonists on H2O2 release by peritoneal macrophages from DA and AO rats were investigated. Met-ENK increased and decreased H2O2 production by macrophages of DA and AO rats, respectively. These effects were antagonized by low, but not high, concentrations of naloxone and ICI 174864. High concentrations of both antagonists directly modulated H2O2 release and retained the strain-related differences seen with Met-ENK. The results showed direct, strain- and dose-dependent, effects of Met-ENK, naloxone, and ICI 174864 on rat macrophage function.