Polymorphonuclear leukocytes (neutrophils) apoptosis is an important mechanism regulating the life span and some functions of neutrophils at inflamed sites. The opioid peptides are present in the peripheral circulation and their concentrations rapidly increase as the result of stress and inflammation. The effect of opioid peptides such as met-enkephalin (M-ENK) and beta-endorphin (beta-END) on tumor necrosis factor alpha (TNF-alpha)-induced apoptosis in human neutrophils in vitro was investigated. Neutrophils isolated from peripheral blood were cultured in the absence or presence of 106-1010 M of opioid peptides for 8, 12 and 18 hours. Features of apoptotic neutrophils were measured by flow cytometric method based on analysis of apoptotic nuclei (DNA content). We found that M-ENK and beta-END enhanced both non-induced and TNF-alpha-induced neutrophil apoptosis in vitro in a dose-dependent manner. The effect of opioid peptides on modulation of neutrophil apoptosis was not reversed by opioid-receptor antagonist naloxone. The results suggest that M-ENK and beta-END can regulate neutrophil life span via apoptosis and in this way may participate in resolution of inflammation.