Whole and nonadherent Peyer's patch cells were shown to present antigen to cloned antigen specific T-cells, albeit less efficiently than spleen cells. Unlike spleen cells, adherent PP cells did not present antigen, and PP lacked cells with classical dendritic morphology. The antigen presenting and MLR-stimulating cell in both spleen and PP were concentrated in the low density (BPA floaters) population. Soluble antigens (OVA, HGG, HSA, and KLH) are poorly presented by PP and do not elicit a T-cell proliferative response in PP when fed orally. These antigens induce oral tolerance and Ts cells in PP, MLN, and spleen. As with systemic tolerance, however, Ts (as measured by adoptive transfer) are not necessary for the induction of tolerance and can be eliminated by colchicine and Cytoxan without a significant effect on the initiation of tolerance. Evidence from studies in various inbred strains of mice suggests that oral tolerance is dependent on genetic factors, but the susceptibility of the strain is different from that induced by the systemic injection of the same antigen. Data are also presented that suggest that in studies of oral tolerance to various antigens, care must be exercised in excluding the effect of diet.