Psoriatic epidermis is characterized by increased DNA synthesis and disturbed differentiation. Even though these processes are closely associated, most investigations do not give insight into temporal/spatial relationships between both events. We previously developed a double labeling method for the simultaneous demonstration of the germinative and differentiated epidermal compartments in normal human skin by using tritium-labeled thymidine ([3H] Thd) incorporation and immunoperoxidase staining of 67 kD keratin polypeptides. In this paper we report the results of combined evaluation of these compartments in stable plaques of psoriasis. Scanning of skin sections with an automatic image analyzer allows objective quantification of areas of total epidermis, 67 kD+ differentiated epidermis and numbers of [3H] Thdr+ nuclei. Our data indicate that the 67 kD- undifferentiated psoriatic epidermis is expanded. Increased numbers of [3H] Thd+ basal and suprabasal psoriatic keratinocytes are present and most of them (97.9%) pertain to the 67 kD- compartment. Keratin identification in scales taken from the same sites showed a variable but distinct decrease of 67 kD keratin polypeptides. Hence, the hyperplastic epidermis of stable plaques of psoriasis is characterized by the presence of increased numbers of [3H] Thd+ cells, which primarily belong to the undifferentiated (67 kD-) basal and suprabasal compartments, especially in the lowermost parts of the elongated interpapillary rete ridges. These changes are associated with a relative decrease of synthesis of 67 kD polypeptides and the presence in the scales of keratins that confer a characteristic hyperproliferative epidermal keratin pattern to the psoriatic plaque.