Vitamin A deficiency clearly has profound effects on the immune system, both in model systems and in human populations, but the effects are very selective. Even where specific antigens elicit a poor response, immune stimulation as measured by other indices might remain intact. A recent study’9 illustrates the complexity of these responses in a human population, by examining T-cell subtypes and their differential responses to supplementation. One attractive hypothesis’a involves a newly discovered metabolite of vitamin A, 14-hydroxy retroretinol (HRR), which is synthesised from retinol by cultured lymphocytes. This metabolite exhibits a strikingly higher specific activity than retinol for lymphocyte regulation, probably by an intracellular signalling activity that is not yet fully understood. The favoured hypothesis’8 is that, whereas in vitro there is partial loss of the normal control of the immunostimulation response such that even a single surface molecule can trigger a response, by contrast in vivo a concerted cooperative action is required from several surface and intracellular receptors to achieve the same result. As a result of this cooperative process, HRR is formed from retinol after stimulation by protein kinase C. HRR then enters the nucleus from the cytoplasm and stimulates mRNA transcription. If confirmed, this hypothesis could lead to a new and exciting explanation of one of the effects of vitamin A on immune function. Although lymphocytes also have receptors for retinoic acid (the probable genome activator in other tissues’O), retinoic acid does not seem to possess exactly the same signalling function as retinol or HRR in lymphocytes. However, retinoids including retinoic acid probably do exert other important effects on immune functions, including differentiation, stimulation of phagocytosis, and modulation of cytokines and eicosanoids. Other studies2’ have raised the possibility that p-carotene may also possess immuno-enhancing effects in some vulnerable groups of people. Clearly this is a promising development in view of the low toxicity of this nutrient, but its importance is not yet clear. Likewise, it is not yet known whether (3-carotene can act without conversion to other retinoids.