We describe herein a patient in whose family 11 of 20 members have a palmoplantar keratoderma. The pathologic findings in the proband were those of epidermolytic hyperkeratosis. As in the other families described, the disease was found to be inherited as an autosomal dominant trait. All involved family members had hyperkeratosis of the palms and soles as infants. Light microscopy showed hyperkeratosis, hypergranulosis with large irregular keratohyalin granules, and large clear spaces in the cells of the granular and upper spinous layers. Our electron microscopic findings showed that the clear spaces were areas of cytoplasm filled with a fibrillar material and cellular organelles; abnormal clumps of tonofilaments and keratohyalin were also present. We consider this disorder to be a form of keratoderma rather than a localized ichthyosis.