The effect of skin tumor promote, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related phorbol esters on primary diploid and four established, i.e. two aneuploid premalignant and two malignant, lines of fetal rat epidermal cells wee analyzed. TPA quantitatively or qualitatively affected the keratinization processes of cultured epidermal cells in the concentration range of 10 - 1,000 ng/ml. Its inhibitory effect on keratinization was obvious in the lamellar keratinization processes of aneuploid premalignant epidermal cells. With a few exceptions, the inhibition was reversible. However, TPA lethally damaged the primary diploid epidermal cells in this range of concentration. TPA did not inhibit the keratinization of malignant epidermal cells but destroyed the polarity in their keratinization processes.