During the course of a lifetime, it has been calculated that we may consume between 100 and 700 tons of food. For the average British citizen, this is likely to include some 550 poultry, 36 pigs, 36 sheep, eight oxen, 10000 eggs and dairy products (milk, butter cheese, etc.) equivalent to 18 tonnes of milk. As if that were not sufficient enough a challenge, the homeostasis within the intestine is further complicated by the presence of 10(5)-10(11) bacteria (pathogenic and non-pathogenic) per gram of mucus and the constant turnover of gut epithelial cells. Given such a magnitude of challenge, which, at least in health is heavily biased in favour of harmless antigens, it can be reasonably hypothesised that the default response of the intestinal mucosal immune system would appear to be set heavily in favour of non-responsiveness and oral tolerance. The purpose of this review is to briefly describe recent progress from studies of the pig that support this hypothesis and to discuss the implications for future mucosal vaccine design.