Nano-and microparticles of poly(lactide-co-glycolide) (PLGA) were formulated using poly(vinyl alcohol) (PVA) or hydrophobically modified hydroxyethylcellulose (HMHEC) or polyethyleneimine (PEI) as stabilizers. The uptake by murine Peyer's patches (PPs) and the binding to Peyer's patches-free tissue (PPFT) of these particles was investigated using fluorescence microscopy providing qualitative information about the tissue distribution of particles. Observations of intestinal cryo-sections showed significant discrimination in the uptake by PP of nano-and microparticles. The uptake by PPs of PLGA-PVA and PLGA-HMHEC nano-and microparticles, of negative and neutral zeta potential, respectively, was comparable, whereas a smaller number was observed in the case of nano-and microparticles of PLGA-PEI, positively charged. Moreover, particle uptake by PPs appeared to be strongly size-dependent. The number of particles of mean diameter around 0.3 and 1 microm observed in PPs was much greater than that of particles of diameter average close to 3 microm. However, in all cases, particles were found in the PPFT for at least 48 h. In conclusion, regarding the tissue samples we have observed, it appeared that the uptake of particles by PPs and binding to PPFT could be influenced by the physicochemical properties of the particles but this may not have been true at all sites of the intestine and may differ between animals.