Hair bulb keratinocytes generate one of the few "immune privileged" tissue compartments of the mammalian organism by suppressing classical MHC class I (MHC Ia) antigens. Expression of non-classical MHC class I (MHC Ib) antigens in the follicle has been found, but only in its distal epithelium. Here, we have defined when during murine hair follicle morphogenesis these peculiar MHC Ia and Ib expression patterns are established, how they change during the murine hair cycle, and how different MHC I modulatory agents alter follicular MHC Ia and Ib expression in vivo. During neonatal hair follicle morphogenesis in C57BL/6 mice, distal follicle keratinocytes began to express MHC Ia (H2b) only late in development. The MHC Ib antigens, Qa-1 and Qa-2, did not become visible until the initiation of follicle cycling, with Qa-1 expression being more widespread than that of Qa-2. H2b, Qa-1, and TAP-1 immunoreactivity on previously negative keratinocytes of the proximal anagen hair bulb was upregulated by intradermal injection of the proinflammatory cytokine interferon-gamma, but not by tumor necrosis factor-alpha or interleukin-1beta. Injection of the reportedly MHC class I downregulating agents interleukin-10, insulin-like growth factor-1, transforming growth factor-beta, alpha-melanocyte stimulating hormone, or dexamethasone, however, all failed to downregulate constitutive or interferon-gamma-induced follicular MHC Ia expression. This shows that the hair follicle is a previously unrecognized site of Qa-1 expression and that interferon-gamma is a key regulator of follicular MHC I expression in vivo. It also suggests that the developmental and immunologic controls of MHC I expression by follicle keratinocytes differ from those of other epithelial cells.