Many epithelia respond to exogenous injurious agents with an increased proliferation. Until now interepithelial cells (neuroectodermal cells, lymphocytes, cerebriform cells and Langerhans cells) have been neglected in investigations of the proliferation kinetics of stratified squamous epithelia. In mice with different antigenic exposure, and in T-cell deficient nude mice mitoses in the oral epithelium were counted by light microscopy and the proportion of mitoses of interepithelial cells was determined by an additional ultrastructural analysis. NMRI mice raised in "germ-free" and "specific pathogen-free" environments exhibit decreased mitotic rates in lingual and buccal epithelia (16 mitoses per 1000 basal cells) when compared with mice raised in "normal" environments. NMRI mice exposed orally to Candida albicans exhibit increased mitotic rates in the same 2 epithelial sites (35 mitoses per 1000 basal cells after 2 days). Similar changes occur in athymic nude mice. The electron microscopic observations showed that most of the mitoses occurred among keratinocytes. Only sporadic mitoses of nonepithelial cells could be observed within the epithelium. However, these amounted to less than 5% of the total of mitoses. Our results show that for proliferation kinetic studies of squamous epithelia this low proportion of interepithelial mitoses may be negligible. Interepithelial cells apparently recruit mainly from migrating cells into the epithelium, while proliferation in situ plays a secondary role. As there are no signs of a transmigration of the epithelium by interepithelial cells they must be considered a recirculating cell population.