At present little is known about the control mechanisms involved in coordinating cell production and maturation in epidermis. To investigate this, we have measured the rate of transit from the proliferative to the terminally differentiating compartment in confluent low-calcium cultures of normal epidermal keratinocytes, using involucrin as a marker of terminal differentiation. We estimate a rate of transit of 3.58 cells/5000 cells/h and a differentiation probability of 0.017, indicating a bias toward self-renewal. Surprisingly, some cells in culture synthesized DNA and expressed involucrin simultaneously. In psoriatic plaques, involucrin expression begins closer to the basal layer than in normal epidermis, and here too we found S-phase involucrin-positive cells. We also observed occasional mitotic involucrin-positive cells in psoriatic epidermis, although we were unable to detect them in culture. Our experiments show that temporal separation of proliferation and terminal differentiation is not obligatory, and thus, the kinetic organization of epidermis may be less rigid than some models imply.