In 19 patients who had retinal vein occlusion or retinal artery occlusion before the age of 50 years, the incidence of hyperhomocysteinemia, as observed in heterozygosity for homocystinuria, was studied by the performance of a standardized, oral methionine-loading test. In four of the 19 patients (21%), two with retinal artery occlusion and two with central retinal vein occlusion, the after-load peak levels of homocysteine exceeded the mean level, established in normal control subjects, by more than two standard deviations and were as well within the ranges established in obligate heterozygotes for homocystinuria. Because the frequency of heterozygosity for homocystinuria in the normal population is one in 70 (1.4%) at the most, we conclude that hyperhomocysteinemia predisposes to the development of premature retinal artery and retinal vein occlusion (P < .01; chi 2 test).