BACKGROUND Blood levels in macular cystoid spaces are commonly seen in patients with branch or central retinal vein obstruction, but have not been previously reported. METHODS To determine blood levels in cystoid spaces, a retrospective study was conducted of 102 eyes with branch retinal vein obstruction, 54 eyes with central retinal vein obstruction, 207 eyes with clinically significant diabetic macular edema, and 109 eyes with aphakic or pseudophakic cystoid macular edema seen over a 5-year period. RESULTS Definite blood levels in cystoid spaces were found in 26 eyes (25%) with branch vein obstruction and in 4 eyes (8%) with central vein obstruction. In contrast, this clinical change was detected in only 1 of 207 eyes (1%) with diabetic cystoid macular edema, and in only 2 of 109 eyes (2%) with aphakic or pseudophakic cystoid macular edema (P < 0.001). When blood levels in cystoid spaces were detected in patients with branch vein obstruction, the site of obstruction tended to be superotemporal (P < 0.05). CONCLUSIONS Blood levels in cystoid spaces are an important sign of retinal vein obstruction, and may help establish the diagnosis in certain cases.