Following loss of small bowel surface area, the remnant intestine undergoes a remarkable adaptive response. To define more fully the underlying molecular mechanisms, we have identified genes that are specifically induced in the adapting remnant after partial small bowel resection. Several of these, including cellular retinol binding protein II (CRBP II) and apolipoprotein (apo) AI, participate in vitamin A and lipid trafficking. The CRBP II and apo A-I promoters contain response elements for the nuclear retinoid X receptor RXR-alpha. It is well established that vitamin A is essential for normal cell growth, differentiation and maintenance of epithelial tissues and that CRBP II functions to facilitate intestinal vitamin A absorption and metabolism. On the basis of these considerations, changes in CRBP II and apo A-I mRNA levels could reflect a role for retinoids in modulating the intestinal adaptive response. To explore this hypothesis, we used a rat resection model of intestinal adaptation to examine the temporal patterns of CRBP II, apo A-I and RXR-alpha expression postresection. CRBP II and apo A-I mRNA levels were increased in the remnant intestine in distinct temporal patterns, whereas RXR-alpha expression was unchanged. To address directly the effects of vitamin A in adaptation, retinoic acid or vehicle was administered intravenously to rats immediately after 70% small bowel resection. Compared with vehicle, all-trans-retinoic acid significantly stimulated crypt cell proliferation in the adapting remnant intestine by 6 h after surgery. These data suggest that retinoic acid acts to modulate intestinal proliferation in the adapting small intestine after loss of functional small bowel surface area.