Adenosine diphosphatase, an endothelial cell ectoenzyme that hydrolyses adenosine 5'-diphosphate to adenosine monophosphate, has been used histochemically to study the human retinal vasculature in flat mounts or as flat-embedded tissue that can be sectioned. In all retinas, reaction product was confined almost exclusively to the vasculature, with arteries having more reaction product than veins or capillaries. Adenosine diphosphatase activity was observed in endothelium, smooth-muscle cells, pericytes, and erythrocytes. In the more elaborate version of the technique, the adenosine diphosphatase-incubated retinas were flat embedded in glycol methacrylate. This allowed study of the retinal vasculature in dual perspective: en bloc with the use of dark-field microscopy and specific areas of interest histologically sectioned for further evaluation. The technique is simple and preserves angioarchitecture because the retinas are intact, and patency of the vasculature can be determined.