Concentrations of plasma 6-keto-prostaglandin F_1α (6-kcto-PGF_1α), a stable metabolite of prostacyclin, were measured by radioimmunoassay before and after 3 min of induced ischemia in 45 diabetics and 23 controls matched for age. In the 45 diabetics, 15 had no vascular complications (group I), 10 had a macroangiopathy (group II), 10 had a microangiopathy (group III) and 10 had both macroangiopathy and microangiopathy (group IV). Plasma levels of 6-keto-PGF_1α; before forearm ischemia were significantly lower in group IV diabetics than in non-diabetic controls (188 ± 17 pg/ml and 245 ± 14 pg/ml, respectively). After 3 min of ischemia, plasma 6-keto-PGF_1α concentrations were increased in control subjects by 34% and by 21% in group I diabetics. In group III diabetics as well as diabetics with atherosclerotic vascular lesions (groups II and IV), no significant change was observed after 3 min of ischemia. These results suggest that impaired vessel wall prostacyclin production may to some extent be responsible for the developmentof diabetic retinopathy and nephropathy as well as atherosclerotic vascular complications.