BACKGROUND Heat shock proteins (HSPs) have a physiologic function in unstressed cells, which is believed to include a role as a "molecular chaperone." The hair cycle is characterized by rhythmic tissue remodelling processes, and is an intriguing model for studying the relation between keratinocyte differentiation and HSP expression under physiologic circumstances. We have therefore studied, by immunofluorescence, the expression of selected HSPs during the murine hair cycle. METHODS The association between hair follicle cycling and the expression of three selected HSPs (HSPs 27, 60, and 72) was examined by immunofluorescence, using the depilation-induced hair cycle of C57BL/6 mice. RESULTS HSP expression was absent from telogen follicles, and was restricted predominantly to keratinocytes in the bulge and the cycling epithelial portion of the hair follicle during anagen and catagen. Immunoreactivity for HSPs 27, 60, and 72 in the hair bulb increased significantly during anagen VI and the catagen transformation of the follicle, and decreased again abruptly with completion of the catagen-telogen transformation. The expression pattern of HSPs 60 and 72 in situ was cytoplasmic, whereas that of HSP 27 was both cytoplasmic and nuclear. CONCLUSIONS These observations suggest that the synthesis of HSPs by hair bulb keratinocytes is related to the anagen-catagen transformation of the follicle, possibly reflecting keratinocyte apoptosis and/or terminal differentiation in the regressing, cycling portion of the follicle. In addition, the rather proximal localization of HSP expression makes it unlikely that the HSPs examined interact with the more distally located intrafollicular gamma/delta T-cell receptor-positive lymphocytes.