Urticaria pigmentosa (UP) developed in two sisters in infancy. The lesions in both patients contained an extensive infiltration of large, tightly packed mast cells. The number of mast cells and the histamine content were increased in the lesions of both patients and also in the clinically normal skin of one subject. A proportion of mast cells in lesional and perilesional skin was found, by light microscopy, to contain giant cytoplasmic granules that, on electron microscopy, were noted to reach a maximum size of about 6 mum in diameter and to have an abnormal ultrastructure. Giant granules were not seen in other cell types, including neutrophils and melanocytes. The findings suggest that genetic factors are important in determining this variant of UP and that the disease may be more widespread in the skin than the eruption indicates.