To investigate the uptake and transport patterns of variously sized particles in Peyer's patches (PPs) of calves, intestinal loops were created in four newborn and two 2-month-old calves, and the loops were inoculated with various particles, including carbon black, fluorescein isothiocyanate (FITC)-labeled latex, FITC-labeled dextran, bovine serum, and recombinant mouse prion protein (rMPrP). The intestinal loops were recovered at 3, 6, 9, and 24 h in newborn calves and at 24 h in 2-month-old calves after inoculation, and the transport of the particles was examined by histological and immunohistochemical means. The uptake of the particles was quantified by estimation of signal intensities. A greater intensity was found in newborn calves compared with the 2-month-old calves. The peak uptake of carbon black, FITC-labeled latex, and rMPrP in the PPs of the distal ileum occurred at 6 h after inoculation in newborn calves and then progressively decreased with time. Uptake was also dependent on the site within the small intestine and the size of the particle studied. The transport of carbon black, FITC-labeled latex, and FITC-labeled dextran occurred via the bloodstream, the mesenteric lymph nodes, and the liver of newborn calves. rMPrP was found primarily in the interfollicular regions of the submucosa of the distal ileum of newborn calves. Thus, distal ileal PPs are probably more effective at particle absorption than the jejunal PPs, and the peak uptake of the PPs within the newborn calf occurs at 6 h after inoculation.