Systemic hemorheologic abnormalities may play a part in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients compared with age-matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at 1 year post-treatment for the treated group compared with the control group (increase of visual acuity of 1.5 lines vs decrease of 1.5 lines). The retinal blood flow parameters were markedly improved soon after the institution of therapy, and this may have contributed to the improvement in visual acuity in the treated group. There was no statistically significant difference between the two groups in the progression to ischemic central vein occlusion.