Background: Intestinal adaptation after loss of functional small bowel surface area is characterized by cellular hyperplasia and increased absorptive function. Interventions to enhance the adaptive response are needed to decrease the morbidity and mortality associated with short bowel syndrome. Retinoic acid was shown to stimulate crypt cell proliferation in the adapting remnant rat ileum by 6 hours after resection. Thus, vitamin A, which is required for normal epithelial cell proliferation and differentiation and which can modulate programmed cell death, may play an important role in the adapting intestine. On the basis of these observations, the effects of vitamin A deficiency on intestinal morphology, epithelial cell proliferation, and apoptosis in the adapting intestine after resection were investigated. Methods: Weanling male Sprague-Dawley rats fed either a vitamin A-deficient or -sufficient diet for 58 days underwent 70% proximal small bowel resection. The deficient rats were divided into cohorts that were either maintained on the experimental diet after surgery or replenished with vitamin A 20 hours before surgery and switched to the control diet after surgery. Results: Ten days after resection, vitamin A-deficient rats exhibited a markedly blunted adaptive response. The adaptive increase in villus height and crypt depth was absent in the deficient rats. However, adaptive increases in crypt cell proliferation were not attenuated by vitamin A deficiency, and there were no differences in apoptotic indices. Conclusions: Vitamin A deficiency inhibits the adaptive response to partial small bowel resection, supporting a role for vitamin A in the adaptive process. Changes in cellular proliferation or programmed cell death are not sufficient to account for this inhibition. This model system will be useful for examining the role of other mechanisms, such as changes in cell-cell and cell-extracellular matrix interactions, and rates of epithelial cell migration and cell extrusion.