Both crude retinal extract and serum contain growth factors for retinal capillary endothelial cells (EC). This study, however, has shown that the combined presence of both crude retinal extract (bovine) and adult serum, induces profound inhibition of EC growth in vitro. EC grown under these conditions develop as sparse colonies of cells which appear to be inhibited from spreading on the fibronectin-coated surface. The extract/serum mixture is not toxic to the cells since it does not affect the viability and typical cobblestone morphology of established confluent cultures. Combinations of retinal extract with adult sera from various species exert the inhibitory effect but foetal or newborn serum is not affected by the extract. Growth inhibition is also found with crude bovine brain extract but cannot be ascribed to the presence of basic fibroblast growth factor (bFGF) or heparin in the extract, nor to a previously identified heat-labile (56 degrees C, 30 min) inhibitory factor in retinal extract. The inhibition is selective for endothelial cells in that mural cells (pericytes) remain unaffected. The nature and relevance of this inhibitory activity remains to be determined.