Membranous epithelial or "M" cells in lymphoid follicle epithelium of Peyer's patches extend between the adjacent columnar cells, forming a membrane separating lymphocytes in the epithelial cell layer from the intestinal lumen. They lack developed microvilli, glycocalyx, or terminal web but contain numerous vesicles. Transport of particles from ligated intestinal loops by such cells without evidence of further uptake of these particles by lymphocytes has been described by others. Horseradish peroxidase (HRP), an enzyme known to function orally and parenterally as a foreign protein antigen, was injected into the unligated intestines of fasted healthy 2-month-old white Swiss mice to determine if HRP would be absorbed in detectable quantities by M cells, and whether subsequent uptake of HRP by lymphocytes could be documented. At intervals from 1 to 60 min the most distal ileal Peyer's patch was fixed, removed, reacted with H2O2-3,3'-diaminobenzidine and examined by light and electron microscopy for HRP reaction product. At 1 min HRP adhered to surfaces of columnar cells and M cells and extended down into surface pits in the M cell. After 5 min HRP was found in vesicles of M cells but not in columnar cells. At 1 hr HRP was detected in the extracellular space between M cells and their enfolded lymphocytes, as well as in vesicles within these lymphocytes. Transport of intestinal luminal material by M cells with subsequent uptake by lymphocytes provides a specific route for antigen uptake into the intestinal lymphoid system.