The levels of the endogenous opioids, β-endorphin and methionine-enkephalin, were analyzed in 21 severely traumatized patients (ISS 32, mortality 42.8%) from a first blood sample drawn at the scene of the injury before resuscitation within 32 ± 16 minutes after the injury and for 8 days after trauma. Additionally, the respiratory burst function of polymorphonuclear neutrophils (PMNs) was assessed and the results were compared with those obtained from 5 healthy control patients undergoing elective surgery with the same analgesic regimen as the multiple trauma patients. Compared with elective surgery anesthesia (controls 3.3, surgery 3.2 fmol/L), the β-endorphin levels on-scene were markedly elevated (survivors 10.1 fmol/L, non-survivors 15.0 fmol/L) (p< 0.05). Methionine-enkephalin levels after trauma were not different from those of the controls. The stimulation of PMNs with different concentrations of the opioids at the first day after trauma gave results comparable with those of the controls. On the third day after trauma the reactivity of PMNs to low opioid concentrations was markedly suppressed to 79.6% of the baseline value (p< 0.05). Endogenous opioids seem to be able to modulate the nonspecific immune-response after trauma.