Recent work suggests that chemically and structurally distinct domains of the interphotoreceptor matrix ("cone matrix sheaths") surround cone photoreceptor outer segments and ellipsoids. This specific regionalization of at least some molecular constituents of the interphotoreceptor matrix may establish a unique cone-associated microenvironment. Previous histochemical and biochemical investigations have shown that a variety of glycosaminoglycans are components of the interphotoreceptor matrix and that the structural integrity of cone sheaths is slightly disrupted by glycosaminoglycan-degrading enzymes. In order to pursue the possibility that specific glycosaminoglycan species establish cone matrix sheath domains, monoclonal antibodies directed against various unsaturated glycosaminoglycans have been screened on sections of primate retina. The results of these studies identify chondroitin 6-sulfate glycosaminoglycan as a specific component of primate cone matrix sheaths.