Endothelin (ET) plays an important role in the pathogenesis of various cardiovascular lesions. To elucidate the pathophysiologic significance of ET in the development of diabetic retinopathy, we determined immunoreactive ET levels in the vitreous fluid collected during vitrectomy in seven patients with non-insulin dependent diabetes mellitus with proliferative diabetic retinopathy and in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD) were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1 pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels may simply reflect severe endothelial injury to the retinal vessels caused by diabetic microangiopathy rather than an important role in diabetic retinopathy.