The responses of the interepithelial lymphocytes (IEL) and aggregated lymph nodules (ALN; Peyer's patches) of the small intestines of 8-week-old pigs to transmissible gastroenteritis virus (TGEV) infection were characterized at 12, 18, and 24 hours after pigs were inoculated. There was no significant difference in numbers of IEL between control and TGEV-infected pigs at 12 and 18 hours. However, in pigs examined at 24 hours, there was a significant decrease in the number of IEL in the duodenum and cranial portion of the jejunum and an increase of IEL numbers in the nuclear level of the intestinal epithelium. Number and distribution were unchanged in the middle portion of the jejunum and the ileum. Microscopic changes in TGEV-infected pigs included microulceration of the dome epithelium (DE) over the ALN, especially in the cranial portion of the intestine, and villous atrophy in the entire length of the small intestine. Generally, TGEV was found by means of peroxidase-antiperoxidase staining in areas where microscopic lesions occurred. Electron microscopy revealed that M cells and ordinary microvillus-covered epithelial cells in the DE embraced one or more lymphocytes, and formed a specialized cell complex or DE complex. Most of the lymphocytes in the DE complex possessed many organelles indicative of an active cell state. The TGEV was found between microvilli, in the cytoplasmic vesicles of M cells and microvillus-covered epithelial cells in the DE, and in the cytoplasm of macrophages and lymphocytes and some degenerated cells of unidentified origin in the domes of the ALN. The virus was also commonly found in cytoplasmic vesicles of macrophages and degenerated cells in the intestinal lumen near the base of the dome of the ALN.