In a double-masked, randomized, placebo-controlled, two-period crossover study, we measured the effect of aspirin on retinal blood flow in 8 type I diabetic patients, 5 with no observable retinopathy, and 3 with 1-10 observable microaneurysms and no other signs of retinopathy. Each patient ingested 1 capsule/day of either aspirin (650 mg) or placebo for 14 days. Following a 1-month washout period, the treatment was reversed. The bidirectional laser Doppler technique and monochromatic photography were used to measure the blood flow rate in a major temporal retinal artery in 1 eye of each patient at baseline and on the 14th day of each treatment period. Retinal blood flow increased following aspirin in 7 of the 8 patients. Using a standard crossover analysis we found a mean aspirin-placebo treatment difference of 21 +/- 17% (mean +/- 95% CI), which was statistically significant (p = 0.03). Retinal blood flow increased following aspirin by 44 +/- 10% (mean +/- SEM) in the 5 patients with no retinopathy (p = 0.04), but only by 8 +/- 10% (n.s.) in the 3 patients with minimal retinopathy.