Increased nonenzymatic glycation of proteins has been implicated in the pathogenesis of diabetic vascular disease. The authors have shown by 3H-NaBH4 reduction of nonenzymatic glycation adducts that endothelial cell membrane proteins undergo increased nonenzymatic glycation in vitro when exposed to elevated concentrations of glucose. Increased nonenzymatic glycation also was found in vivo for microvascular endothelial cells isolated from streptozotocin-induced diabetic rats compared with control rats. Cultured monocytes have previously been reported to express receptors for certain nonenzymatic glycation adducts. The authors have further investigated whether monocyte interactions with endothelium are altered by the presence of nonenzymatic glycation adducts on endothelium. Adherence assays were performed in the presence of elevated concentrations of glucose with decreased NaCl levels to maintain normal osmolarity (as occurs physiologically). Although monocyte adherence to endothelium and levels of early nonenzymatic glycation adducts increased under these conditions, the increased adherence appears to be due to the altered NaCl levels. In fact, freshly isolated monocytes (in contrast to what has been found for macrophages and activated monocytes) were shown not to express appreciable numbers of receptors for nonenzymatic glycation adducts.