Human skin grafted on to athymic nude mice (BALB/C-nu/nu) spontaneously hyperpigments. We wished to identify the morphological and molecular bases for the hyperpigmentation for this phenomenon. We present data on the relationship of healing, regeneration of melanocytes and production of some melanogenic stimuli. Biopsies were taken at preset times post-graft and studied by histological and immunohistochemical methods. DOPA-positive melanocytes first became visible 120 h post-graft and melanin deposition became visible along the basal cell layer 2 weeks post-graft and increased in quantity with time. By immunochemical stains the quantity of three melanocyte specific enzymes, i.e. tyrosinase, tyrosinase-related protein-1 (TRP-1) and DOPA-chrome tautomerase (TRP-2), was markedly enhanced 1 week after grafting and persisted until 4 weeks post-graft. alpha-Melanocyte-stimulating hormone and adrenocorticotrophic hormone were clearly detected in the epidermis soon after grafting. They were still strongly detected in the epidermis and in the dermis 2-4 weeks post-graft. We conclude that hyperpigmentation in the grafted skin accompanies a marked increase in the quantity of melanogenic enzymes and melanogenic peptides. The neuropeptides might be one of many factors which stimulate melanogenesis.