To develop a vaccine against Escherichia coli-induced post-weaning diarrhea and edema disease, insights in the induction of the protective immune response following infection with these pathogenic E. coli is needed. Therefore, the fimbriae-specific antibody response of newly weaned pigs following infection with the Shiga-like toxin type II variant (SLT-IIv) producing F18(+) verotoxigenic E. coli (VTEC) (strain 107/86) was compared with the response following an infection with LT producing F4(+) enterotoxigenic E. coli (ETEC) (strain GIS 26). F4(+) ETEC were able to colonize the gut very soon after infection, as peak excretion of F4(+) E. coli bacteria was seen 2 days post-infection (dpi), but had already disappeared 7dpi. On the other hand, F18(+) VTEC infection resulted in a slower colonization of the gut as the peak excretion of F18(+) E. coli was observed between 3 and 5dpi, but this colonization remained longer as F18(+) E. coli were detected till 9dpi in feces. Furthermore, this fast colonization pattern of F4(+) ETEC is accompanied with the presence of F4-specific antibodies in mucosal tissues and serum from 4dpi onward, with maximal amounts of F4-specific IgA in the jejunal lamina propria and serum 7dpi. In contrast, F18-specific IgA was only readily detected in the jejunal lamina propria 15dpi and showed a maximum serum titer 21dpi. Besides this faster induction and higher antibody response, the switch from IgM to IgA and IgG was also earlier following the F4(+) ETEC infection.