Culture in the presence of delipidized serum (i.e., in the absence of vitamin A) has been shown to allow terminal differentiation of human keratinocytes, both in terms of morphological appearance and in terms of 67 kD keratin polypeptide synthesis (Fuchs, E & Green, H, Cell 25 1981 617) . Culture at the liquid-air interface is known to induce morphological differentiation in a variety of culture systems designed for keratinocytes (Pruniéras, M et al., J invest dermatol 81 1983 28s). We report here that human keratinocytes grown on a dermal equivalent (or lattice) in the presence of total serum are able to express the 67 kD keratin polypeptide, provided that the culture is raised at the liquid-air interface. Loss of contact with air results in switching off this synthesis.