The distribution of beta-galactoside alpha 2,6-sialyltransferase (alpha 2,6-ST) mRNA in the retina was examined using in situ hybridization histochemistry to study the relation of sialic acid to retinal glycoconjugates. In rod-dominant rat retinas, the alpha 2,6-ST, which was found to be newly expressed in the photoreceptor inner segments on post-natal day (P) 16, appears to sialylate the rod-associated interphotoreceptor matrix (IPM). In cone-dominant squirrel retinas, alpha 2,6-ST mRNA was sparse, which suggests that cone-associated IPM does not contain sialic acids. The light-response of the IPM first occurred between P14 and P16. The IPM around cone photoreceptors did not show the response. These observations suggest that the presence of sialic acids on the termini of sugar chains around rods plays an important role in generating the light response of the IPM. The electrical resistance of the IPM is increased by removing sialic acids from the glycoconjugates of the IPM. The electrical resistance of the rod-associated sialo-IPM may be lower than that of the cone-associated asialo-IPM. The light response of the rod-associated IPM may not only facilitate the transfer of substances between rod photoreceptors and the retinal pigment epithelium, but may also be involved in the generation of the physiological features of rods. A different distribution of alpha 2,6-ST mRNA was detected in light-adapted and dark-adapted rat retinas. The mRNA was diffusely distributed through-out the inner segments in light-adapted retinas, but it was scarce in basal inner segments in dark-adapted ones. The second phase of the IPM-light response, histologically detected as accumulation of the IPM around inner segments, may be induced by an increase in the synthesis of N-glycoside linked glycoconjugates containing sialic acids. Comparing this and the electron microscopic examination of free ribosomes in the inner segments, the dispersed and clustered ribosomes correspond to active and inactive types, respectively. A progressive decrease in the mRNA-expression of alpha 2,6-ST was commonly observed in the process of various types of retinal degeneration.