LTB provokes a systemic immune response and exerts adjuvant effects on mucosal immune responses to unrelated antigens. The binding and uptake of fluorescein-labelled LTB in the normal villus epithelium was compared to that in Peyer's patch dome epithelium in mouse intestine. LTB was bound by the GM1-receptor and taken up extensively by both tissues, indicating that not only the Peyer's patches but also the normal villus epithelium play a significant role in the transport of orally administered antigens. These results were supported by transport studies in the human intestinal epithelial cell line Caco-2 using 125I-LTB. After 2 h incubation, 5.1 +/- 0.1% and 5.9 +/- 0.1% of the added radioactivity was transported in the apical to basolateral and basolateral to apical direction, respectively. Less than 1% of the transported radioactivity was immunoprecipitated with anti-LTB antiserum indicating that LTB was extensively degraded during the transport. The results suggest that normal enterocytes play a significant role in the binding, uptake and transport of orally administered LTB.