OBJECTIVE To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8–12.7 pM]; P < 0.01) and the microalbuminuric patients (10.2 pM [range 5.6–31.1 pM]; P < 0.001) compared with control subjects (6.1 pM [range 4.5–7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P < 0.05). CONCLUSIONS The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.