It has been demonstrated that morphine stimulates the replication of human immunodeficiency virus in peripheral blood mononuclear cells as well as in Kupffer cells. Since the mechanism of action of this drug is still unknown, we have studied its effects on different properties of isolated human blood monocytes. In the presence of morphine, cultured monocytes showed an increase in the fluidity of their membranes as well as an inhibition in their capacity to differentiate into macrophages. Furthermore, the response of the cells to interferon-gamma was significantly decreased and the release of superoxide anions was altered. Finally the production of interferon-alpha and of prostaglandin E2 induced by stimulation of the cells with endotoxin (LPS) was diminished. We conclude that morphine decreases the functions of monocytes that are essential for their antiviral defence and inhibits their response to activating stimuli, which may explain the increased multiplication of HIV in morphine treated monocytes. (C) 1997 International Society for Immunopharmacology.