Ornithine decarboxylase (ODC EC 4.1.1.17) induction in mouse epidermis after single or multiple topical applications of chrysarobin differed from that following topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Following a single application of 220 nmol chrysarobin, ODC activity began to rise at 24 h reaching a peak at 56 h and returned to normal after 96 h. When 5 separate applications of 220 nmol chrysarobin were applied in multiple application protocols, an alteration in the ODC induction response was observed. With a once per week or twice per week application protocol, ODC was elevated in a multiphasic manner giving multiple peaks of activity after the last application. Interestingly, the magnitude of ODC induction was greater using the once per week, compared to the twice per week, application protocol. Preliminary results indicate that a once per week application protocol is more effective than a twice per week protocol for promoting the development of skin papillomas in SENCAR mice. Thus, the magnitude of the induced ODC response with chrysarobin, although low compared to TPA, correlated with tumor promoting activity.