PURPOSE. To determine whether the human retinal oxygenation response response (Delta PO2) to a hyperoxic provocation is abnormal in patients with type I diabetes. METHODS. Magnetic resonance imaging (MRI) was used to measure Delta PO2 during 100% oxygen breathing in patients with type I diabetes who had either no clinically detectable retinopathy (n = 5) or mild to moderate background diabetic retinopathy (BDR; n = 5) and in age-matched healthy control Subjects (n = 7). RESULTS. Both the patients with diabetes and the control subjects exhibited a significant (P < 0.05) increase in the preretinal vitreous signal intensity on changing from room air breathing to oxygen inhalation (i.e., 5 minutes). However, only,9 diabetic patients demonstrated significant (P < 0.05) increases in Delta PO2 between measurements made at 5 minutes of oxygen inhalation and measurements at longer durations of hyperoxia (15, 25, and 35 minutes). Furthermore, Delta PO2 was significantly (P < 0.05) greater in patients with diabetes than in control subjects, but there was no significant difference in Delta PO2 (P > 0.05) between patients with diabetes, with or without retinopathy. Age and Delta PO2 correlated significantly (P < 0.05) in control Subjects but not in patients with diabetes. In control Subjects, Delta PO2 was relatively uniform panretinally, whereas in the diabetic group, changes in oxygenation response were spatially inhomogeneous. CONCLUSIONS. These results demonstrate, for the first time, that MRI Delta PO2 detects a significant Supernormal retinal oxygenation response in patients with type I diabetes, even before the appearance of retinopathy. This study raises the possibility of using MRI measurements of ZAPO, to monitor therapeutic efficacy in human trials.