Scleral tissue from two cases of nanophthalmos was examined by amino acid analysis, light microscopy, histochemistry, and transmission electron microscopy. Perifibrillar aggregates, similar to proteoglycans, were prominent in the nanophthalmic sclera. The sclerae were thicker than normal and the bundles of collagen fibrils were less ordered. The clinical features of vortex vein compression seem causally related to the disordered and thickened sclera, which, in turn, may be caused by dysfunctional proteoglycans, or interaction with the scleral collagen, or both.