To determine the effect of normoglycemia on renal prostaglandin synthesis and renin-angiotensin system activity, prostaglandin E₂ (PGE₂) urinary excretion, plasma renin activity (PRA), and glomerular filtration rate (GFR) were studied in seven patients with insulin-dependent diabetes mellitus (IDDM) without complications, both in basal conditions and after a 20-h treatment with an artificial pancreas. Normoglycemia induced a significant reduction in PGE₂ excretion (88 ± 23 vs. 55 ± 25 ng/12 h, P < .05) and GFR (138 ± 34 vs. 105 ± 20 ml · min⁻¹ · 1.73 m⁻², P < .05) and a nonsignificant increment of PRA (0.52 ± 0.48 vs. 0.83 ± 0.92 ng · ml⁻¹ · h⁻¹). The results enhance the hypothesis that renal prostaglandins play a role in the renal functional alterations observed in IDDM during hyperglycemia.