Melanocyte counts of the café au lait spots of patients without neurofibromatosis and patients with neurofibromatosis are reported. The café au lait spots of patients with neurofibromatosis contain more DOPA-positive melanocytes per square millimeter than does their surrounding skin. The melanocytes are grossly normal but do contain giant pigment granules. Café au lait spots in the patients without neurofibromatosis contained fewer DOPA-positive melanocytes per square millimeter than did the surrounding skin. Giant pigment granules were not found in any of the specimens studied. The finding of giant granules and an increased number of melanocytes in café au lait spots is an invaluable aid in establishing the diagnosis of neurofibromatosis when only pigmented macules are present.