We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the ‘hygiene hypothesis’, is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co-exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention.