During keratinocyte maturation, individual cells undergo an orderly succession of biochemical and structural changes. In certain skin disorders alterations in keratinocyte numbers, volumes, and epidermal skin thickness occur. To assess such alterations and to provide base line values for normal human epidermis, a computer assisted histologic technique was developed. Skin biopsies were taken from normal skin on the forearm, back and thigh of 6 adult men. Whole specimens of epidermis were separated from the dermis with collagenase, fixed, stained, and mounted for microscopic examination. From the three dimensional coordinates of epidermal nuclei, epidermal cell volumes, surface density of epidermal cells, and epidermal thickness were determined. Measurement of cell volumes in this way compared favorably with electronic cell sizing of disaggregated epidermal cells in matched samples. The mean densities of nucleated cells per 10(4) mu2 surface area were 452, 483, and 487 for the forearm, back and thigh respectively. This technique will be used to make similar assessments in disorders of abnormal keratinocyte maturation.