Normal mouse epidermis constitutively expresses prostaglandin-H synthase 1 (PGHS-1) but no PGHS-2. Acute inflammation and epidermal hyperplasia, (hyperplastic transformation), as evoked in adult mouse skin in vivo by wounding or by the phorbol ester phorbol 12-myristate 13-acetate (PMA), resulted in a transient induction of PGHS-2 expression while PGHS-1 remained unchanged. Under conditions of a stationary epidermal hyperplasia, as in neonatal mouse epidermis, PGHS-1, but not PGHS-2, expression was observed. Induction of 'balanced hyperproliferation' by 4-O-methyl-phorbol 12-myristate 13-acetate (4-O-methyl-PMA) did not lead to PGHS-2 expression. When keratinocytes were isolated from neonatal mouse skin and separated by Percoll density-gradient centrifugation according to their stage of differentiation, PGHS-1 mRNA expression and protein were found to be highest in the differentiated cells compared with those from the proliferative compartment. A similar distribution of PGHS-1 mRNA was found in keratinocytes from adult mice, whereas PGHS-1 protein was equally distributed in all cell types. Contrary to the situation in intact epidermis, PGHS-2 mRNA but no protein was detected in all cell fractions. Established keratinocyte lines constitutively expressed both isoenzymes at different ratios. In the mouse line MSCP5 an almost exclusive expression of PGHS-2 was found, which was further enhanced by PMA treatment. These data indicate that the expression of PGHS-2 in mouse epidermis is specifically related to the emergency reaction of hyperplastic transformation.