Annexin I is a calcium- and phospholipid-binding protein that is involved in the regulation of cellular differentiation. The aim of the present study was to determine the localization of annexin I mRNA expression in normal and diseased human skin. In situ hybridization with a specific digoxigenin-labelled RNA probe was used throughout. We detected no annexin I mRNA signals in basal and suprabasal cells of normal epidermis, but positive signals were evident in the sudoriferous ducts. Annexin I mRNA expression was detected in the keratinizing squamous cells in keratotic type seborrhoeic keratosis and in keratinocytes at the periphery of the horn pearl in well-differentiated squamous cell carcinoma. Positive signals were also seen at the border between involved and noninvolved skin in psoriasis vulgaris and in dyskeratotic epidermal keratinocytes in keratosis follicularis Darier. By contrast, no annexin I mRNA signals were detected in tumour cells in basal cell carcinoma. The present results suggest that annexin I expression is related to, and may play a role in, keratinization disorders.