Intestinal barrier function in mice was assessed after acute or chronic oral administration of 15.8‐ and 5. 7‐μm synthetic spherical particles. The results failed to confirm previous reports that ingested particles rapidly appear in blood. Furthermore, 15.8‐μm particles did not accumulate in intestinal Peyer's patches, mesenteric lymph nodes, or other organs of the reticuloendothelial system, even after the maximum dosage of 8 × 10 ⁶ particles per day for 60 d. However, the 5. 7‐μm particles were demonstrated in Peyer's patches, mesenteric lymph nodes, and lungs after the maximum dosage of 4.5 × 10 ⁸ particles per day for 60 d. At 77 d after the termination of ingestion, 5.7‐μm particles were still present in these tissues. The 5.7‐μm particles were not found in spleen; retention in liver was equivocal. The site of uptake of particles capable of penetrating the intestinal mucosa appears to be the Peyer's patches. It is suggested that most absorbed particles are sequestered in Peyer's patch macrophages. Particles that escape sequestration are transported by lymph rather than by portal blood. The findings indicate that hazards associated with intestinal uptake of large (> 5 μm) particulates exist, but that the frequency of such penetration is still unclear.