Background: α-Melanocyte stimulating hormone (α-MSH) is a well-tolerated immunomodulator with cytoprotective and anti-inflammatory effects that is known to stimulate melanogenesis and proliferation of follicular melanocytes. As human hair follicles (HFs) locally synthesize α-MSH, pharmacologically more easily handled α-MSH-related tripeptides, such as K(D)PT, may imitate this endogenous regulation, and may show a favourable side-effect profile on clinical use. Objectives: To investigate the effect of the synthetic, α-MSH-related peptide K(D)PT [which is identical to interleukin (IL)-1β193-195] on melanogenesis in human anagen HFs, under normal and proinflammatory growth conditions. Methods: Normal human anagen VI scalp HFs were microdissected and organ cultured with different concentrations of K(D)PT with or without coadministration of a proinflammatory, catagen-inducing stimulus, interferon (INF)-γ. Masson-Fontana histochemistry and NKI/beteb immunohistochemistry were employed to assess changes in the degree of human HF pigmentation and melanocyte dendricity. Results: As confirmed by quantitative (immuno-)histomorphometry, compared with controls, K(D)PT alone did not affect human HF pigmentation in organ culture. However, in the presence of a strong, prototypic proinflammatory stimulus (IFN-γ), K(D)PT significantly stimulated HF melanin content and melanocyte dendrite formation in situ. Conclusions: The IL-1β- and α-MSH-related tripeptide, K(D)PT, displays interesting hair pigmentation-stimulatory activities under proinflammatory conditions. These might become exploitable for innovative antigreying strategies, notably in postinflammatory poliosis (regrowth of white hair, e.g. during recovery from alopecia areata), where no effective clinical therapy is yet available. © 2008 The Authors.