The cotton-wool spot is a common fundus finding in patients with many ocular and systemic diseases. We investigated the characteristics of cotton-wool spots in patients with four major diseases, ie, acquired immunodeficiency syndrome, diabetes mellitus, systemic hypertension, and central retinal vein occlusion, to see if any differences were detected in their number, size, or location. A composite of all the cotton-wool spots for each of these four categories was obtained by computed reconstruction to analyze variations in their distribution and size. The cotton-wool spots had a predilection for the temporal quadrants in the four categories and were smaller in patients with acquired immunodeficiency syndrome than the other groups. Patients with ischemic central retinal vein occlusion had more cotton-wool spots than the other groups. No other definite differences were detected. Cotton-wool spots than the other groups. No other definite differences were detected. Cotton-wool spots seem to be a common pathway following various insults to the retina, most probably of a vaso-occlusive origin.