Normal human epidermal melanocytes became swollen and more dendritec and the immunoreactive tyrosinase increased markedly when they were cultured for 2 days with 5 ,u M of histamine. These results suggest that high dermal concentrations of histamine may be responsible for the induction of skin pigmentary changes associated with local proliferation of mast cells such as in urticaria pigmentosa and systemic mastocytosis.histamine ; melanocyte ; skin pigmentation ; tyrosinase ; urticaria pigmentosa Melanocytes have a highly specialized function to make melanin pigment in the skin. Although hyperpigmentation is characteristic of skin lesions of urticaria pigmentosa in which mast cells proliferate massively in the dermis, its pathomechanism for hyperpigmentation has not been clarified yet. Mast cells are well known to release histamine by noxious and immunological stimuli and high concentrations of histamine were detected in the skin lesions of urticaria pigmentosa (Greaves and Sondergaard 1970;Granerus et al. 1983). Thus, it is reasonable to speculate that histamine may stimulate the melanocytes to induce hyperpigmentation in the skin lesions of urticaria pigmentosa. In this report we show for the first time that histamine has a direct stimulatory effect on normal human melanocytes in vitro.Human melanocytes from the roof of suction blisters were cultured as described previously (Tomita et al. 1987). Immunofluorescent staining of cultured melanocytes was carried out using rat monoclonal antibody against tyrosinase and fluorescein isothiocyanate (FITC)-conjugated second antibody directed to the monoclonal antibody