Acute exposure of human saphenous vein or internal thoracic artery endothelium to either morphine [27.4 +/- 3.7 and 35.4 +/- 4.1 nM nitric oxide (NO), respectively] or anandamide (18.3 +/- 2.2 and 24.3 +/- 3.0 nM, respectively) results in NO release, whereas exposure to the human immunodeficiency virus envelope protein gp120 does not. After the short-term exposure of the vessel endothelium, monocyte adherence is diminished with morphine and anandamide treatment (jointly by -80%), whereas it is enhanced with that of gp120 (approximately 40%), indicating that gp120 enhances the ability of the endothelium to adhere monocytes. Long-term or continuous exposure of the endothelia to all agents results in a significant enhancement of monocyte adherence (p < 0.05), which is further increased when exposed to either morphine and anandamide plus gp120. This is caused by a desensitization of the endothelium to further NO release after the initial exposure to either anandamide or morphine. The results serve to indicate that in individuals abusing opiates and or cannabinoids, a tissue [i.e., central nervous system (CNS)] viral load may be higher, and acquired immunodeficiency syndrome (AIDS) may progress more rapidly because monocyte adherence and mobility is significantly increased, indicating a higher level of transmembrane migration.