Until recently, vitamin A research was focused primarily on preventing xerophthalmia and blindness in third world countries and on development of synthetic retinoids with lower toxicity than vitamin A for treatment of skin diseases. During the past five to ten years, however, there has been a dramatic shift in emphasis. Mortality, primarily from infectious disease, has been identified as an important accompaniment of xerophthalmia, and has now proved to be responsive to the massive intermittent vitamin A dosage schedules that were originally introduced to combat blindness. These results raise the possibility that vitamin A influences specific elements of the immune system. There has also been growing concern about dietary and environmental substances that cause long-term tissue damage, particularly to the genome, and thus increase the risk of cancer and other degenerative diseases. According to one hypothesis certain nutrients, including the carotenoids, may help to reduce this damage. Such protection is separate from the well-established role of some carotenoids as metabolic precursors of vitamin A, and may involve antioxidant protection against oxidative free radical attack.