Café au lait spots from 14 Japanese patients with neurofibromatosis and nevus spilus from 9 Japanese patients were subjected to the studies on the differences in nature of their melanocytes. When the number of melanocytes of the pigmented lesions was compared with that of the surrounding normal skin, the former was always increased and that of café au lait spot was higher than that of nevus spilus. Giant pigment granules were recognized only in 6 patients out of 14 with neurofibromatosis but not in nevus spilus examined. 2 days after UV irradiation at 4 MED, the number of melanocytes was increased in both surrounding normal skin and pigmented lesion, and the rates of increase were lower in the pigmented lesion. Under the electron microscope, melanocytes in cafe au lait spots which received an ultraviolet light irradiation showed various changes in their cytoplasm ; a development of dendrites containing many mature melanosomes, an increased number of cytoplasmic vacuoles and mitochondria, a development of Golgi apparatus in their cytoplasm, appearances of some dense-bodies and of autophagosomal melanosome-complexes. In nevus spilus, the same kind of changes occurred, but they were moderate com-pared with those developed in cafe au lait spots. Melanosomes in the keratinocytes of café au lait spots tended to come together around the nucleus and to form melanosome-complexes; while, melanosomes in the keratinocytes of nevus spilus seemed to be single-dispersed after irradiation. The causative factors of the hyperpigmentation and the different reactivity of melanocytes against UV irradiation in these two pigmented macules were discussed.