Intestinal intraepithelial lymphocytes are a large and heterogenous population of lymphocytes located strategically at the entry site of enteric pathogens into the body. Their ability to proliferate and produce interferon-gamma in vitro in response to mitogens or interleukin-2 was investigated in four-week-old calves. It was found that they had similar mitogen-induced blastogenic responses and produced interferon-gamma like the peripheral blood lymphocytes of four-week-old calves. Preliminary studies indicated that the intraepithelial lymphocytes also responded to Cryptosporidium parvum antigen in vitro. Thus, intraepithelial lymphocytes may be important in the host's response to enteric infections of calves such as cryptosporidiosis.