Application of 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) to the skin of female CD-1 mice led to a rapid increase in the concentration of epidermal ornithine decarboxylase (ODC) mRNA from an undetectable level in control mice to a high maximum level at 4-5 h after TPA administration. The concentration of epidermal ODC mRNA then decreased rapidly during the next 5 h. The time course for TPA-induced increases in epidermal ODC enzyme activity paralleled very closely the time course for TPA-induced increases in ODC mRNA. Topical administration of 1, 3 or 10 mumol curcumin together with 5 nmol TPA inhibited by 66, 81 and 91% respectively TPA-induced increases in epidermal ODC enzyme activity measured 5 h later. In a parallel study, TPA-induced increases in the concentration of epidermal ODC mRNA was inhibited by 54, 85 and 82% respectively. Intraperitoneal injection of 10 or 30 mumol curcumin 1h before topical application of 5 nmol TPA inhibited TPA-induced increases in epidermal ODC enzyme activity by 75 or 89% respectively. In a parallel study, the induction of epidermal ODC mRNA was inhibited by 53 and 65% respectively. The results indicate that curcumin inhibits TPA-induced increases in epidermal ODC enzyme activity by inhibiting the synthesis and/or enhancing the breakdown of ODC mRNA.