Human CD38 is a 45 kD ectoenzyme endowed with ADP-ribosyl cyclase and hydrolase activities. The molecule plays a central role in lymphocyte activation, proliferation and selectin-type adhesion with endothelial cells (HEC). A HEC surface molecule displaying all the features of a CD38L has been identified by means of a mAb (Moon-1), able to block CD38-mediated adhesion processes. The 130 kD molecule recognized by Moon-1 is CD31, a member of the Ig superfamily. This paper reports on the analysis of the surface expression of CD38 and CD38L in various human tissues of adult origin and compared in some instances to the fetal (9-14 weeks) counterparts. This was achieved by means of immunohistochemical techniques and analysis of purified cell populations. Among the specimens analyzed, CD38 is expressed by a vast array of cells of lymphatic origin as well as by the skeletal and cardiac muscle fibers, the bronchi (epithelial cells), the parotid gland (ductal epithelial cells) and hepatic sinusoids. On the contrary, CD31 proved constantly expressed by HEC at high levels, independent of the organ or tissue analyzed or of the kind of vessel. Other cells expressing CD38L were found in the lymphoid compartment (follicle mantle B cells and plasma cells), in the lungs (alveolar ducts, alveoli and lymphatic vessels) and in the kidney (glomerular cells). Interestingly, no fetal organ or tissue ever expressed CD38 and its ligand. The above results were enriched by the analysis of the expression of the two molecules on purified populations including mononuclear cells from the lamina propria of the gastro-intestinal tract and broncho-alveolar lavage lymphocytes.