The 67N strain of haemagglutinating encephalomyelitis virus (HEV) was inoculated orally or nasally into ten 3-day-old gnotobiotic piglets. Tonsillar changes characterized by epithelial degeneration and lymphatic cell infiltration occurred in the crypt from post-inoculation days (PID) 5 to 7, and HEV was isolated from the tonsil on PID 3 and 5. Ultrastructurally, many HEV particles were found in the cisternae, cytoplasmic vesicules and extracellular spaces of crypt epithelium. Immunohistologically, many HEV particles were observed in the crypt epithelial cells in the early stage of infection. Thereafter, a large number of immunoglobulin (IgG, IgM and IgA)-containing cells were observed in the tonsil. The appearance of IgM-containing cells was coincident with the detection of neutralizing antibody in the serum. These findings suggest that HEV replication in the crypt epithelium stimulates the proliferative response of immunoglobulin (IgG, IgM and IgA)-producing cells.