Tissue growth may be controlled by negative feedback mechanisms. Recently, a pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH ('epidermal pentapeptide', EPP), which slows the growth of mouse epidermis in vivo and of mouse keratinocytes in vitro, was isolated from mouse epidermis. Since inhibitory molecules like EPP might be part of the feedback systems underlying hair growth control, we assessed the effect of synthesized EPP on the growth of hair follicles, using rodent in vivo and in vitro assays. We report for the first time that intraperitoneally injected EPP (30 nmol/animal/day over 6 days) significantly slows the growth of hair follicles in plucking-induced anagen skin of C57 B1-6 mice (as assessed by microscopic morphometry). Using an in vitro organ culture assay, EPP inhibits the incorporation of 3H-thymidine into mouse pelage anagen follicles. That this epidermal-derived peptide affects hair growth raises the possibility that hair growth may be regulated by an inhibition/disinhibition mechanism under participation of EPP-like molecules and that the epidermis may play a role in the control of hair growth.