The effects of naturally occurring sweetening agents, which inhibited the induction of Epstein-Barr virus-associated early antigen (EBV-EA) induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and related compounds on the induction of ornithine decarboxylase (ODC) by TPA is examined. Application of glycyrrhetinic acid or steviol to mouse skin 1 h before TPA treatment showed a remarkable decrease in TPA-induced ODC activity. Post-treatment with glycyrrhetinic acid or steviol 1 h after application of TPA also resulted in a considerable depression in the induction of ODC activity. Neither glycyrrhetinic acid nor steviol alone induced epidermal ODC activity. These results suggest that glycyrrhetinic acid and steviol interfere with the process of induction of epidermal ODC by TPA treatment of mouse skin. cis-Abienol, frullanolide and norambreinolide, which have a partially similar structure in the moiety with glycyrrhetinic acid or steviol, were tested. cis-Abienol and frullanolide showed an inhibitory effect when applied 1 h before TPA treatment, but norambreinolide was not effective. A relationship between suppression of ODC activity and inhibition of EBV-EA induction is discussed.