In one case of naevus verrucosus bilateralis the process of granular degeneration was studied with histological, electronmicroscopical, histochemical and autoradiographic methods. The following results were obtained: 1. There is no indication of an increased epidermopoesis in spite of the acanthotic-hyperkeratotic epidermal thickening. 2. Comparison between paraffin- and cryostat-sections revealed that the reticular aspect of altered cell complexes in granular degeneration is an artefact. 3. The cells of the granular degeneration are characterized by increasing accumulation of irregular basophilic gram-positive material around the nucleus. Electronmicroscopically this material consists of malformed prematurely aggregated tonofilament bundles, which are in connection with desmosomes. In the more superficial cell layers keratohyalin becomes combined with these tonofilament bundles. 4. These results together with the occurence of esterases, acid phosphatases and NADPH-producing enzymes indicate premature and pathological keratinization. 5. The horny cells show pathological configuration, pathological cell content, pathological intercellular connections and pathological intercellular material. These changes are thought to be responsible for the increased stickiness of the horny lamelles at the skin surface. 6. Alterations of the cytoplasmic structure, reduction of 3H-uridine uptake into affected cells and histochemical-enzymatic investigations of the energy-producing metabolism indicate correlated reduction of the cellular metabolic activity. 7. Histological alterations (light- and electronmicroscopically) of granular degeneration in naevus verrucosus are quite similar to those in erythrodermie ichthyosiforme congénitale, although the proliferating and metabolic activity of the epidermis in both diseases seems to be different. It is concluded that granular degeneration can occur under conditions of different metabolic situations of the epidermis. © 1969 Springer-Verlag.