Consumption of food or feed contaminated with fumonisin B(1) (FB(1)), a mycotoxin produced by Fusarium verticillioides, can lead to disease in humans and animals. The present study was conducted to examine the effect of FB1 intake on the intestinal immune system. Piglets were used as a target and as a model species for humans since their gastro-intestinal tract is very similar. The animals were orally exposed to a low dose of FB(1) (1 mg/kg body weight FB(1)) for 10 days which did not result in clinical signs. However, when compared to non-exposed animals, FB(1)-exposed animals showed a longer shedding of F4(+) enterotoxigenic Escherichia coli (ETEC) following infection and a lower induction of the antigen-specific immune response following oral immunization. Further analyses to elucidate the mechanisms behind these observations revealed a reduced intestinal expression of IL-12p40, an impaired function of intestinal antigen presenting cells (APC), with decreased upregulation of Major Histocompatibility Complex Class II molecule (MHC-II) and reduced T cell stimulatory capacity upon stimulation. Taken together, these results indicate an FB(1)-mediated reduction of in vivo APC maturation.