A retinoid-binding protein has been identified in the extracellular space that separates the photoreceptor cells and the retinal pigment epithelium (RPE) of the mammalian retina. This protein (interphotoreceptor retinoid-binding protein, IRBP) appears to be involved in the transport of visual cycle retinoids between the photoreceptors and the RPE. Experiments were conducted to evaluate the possibility that the amount of IRBP in the retina is regulated by the availability of retinoids in the retina. Rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After 23 weeks, when rhodopsin levels had declined by over 90% in the -A rats, some animals in the latter group were given a single intramuscular injection of all-trans retinol. Both 1 day and 1 week later, the IRBP immunoreactivities in the retinas from the treated rats were determined with quantitative immunocytochemistry. IRBP immunolabeling densities were also determined in the +A and -A groups. Retinas of animals that had consumed the -A diet for 23 weeks bound an average of 50% less anti-IRBP antibody in the retina than rats that had been fed the +A diet for the same period. One day after retinol administration, the mean IRBP immunolabeling density had returned to that observed in the +A rats. The restored level of IRBP immunoreactivity was maintained 1 week after injection. The immunocytochemical findings were confirmed by immunoblot analysis of eyecup homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)