Curcumin is a major chemical constituent of turmeric normally eaten by humans. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) is a strong promoter of chemically induced skin cancer. The exact mechanism by which TPA promotes skin cancer is not clear. However, it is known that TPA elevates the expression of oncogenes involved in cell proliferation. Recently, it has been shown that turmeric or curcumin significantly inhibits TPA-induced tumor promotion on mouse skin. However, the mechanism by which curcumin inhibits TPA-induced tumor promotion is not known. In the present studies, we investigated the effect of curcumin on the expression of c-fos, c-jun and c-myc oncogenes in TPA-treated mouse skin in CD-1 mice. A 30-nmol dose of TPA increased the levels of mRNAs for c-fos, c-jun and c-myc oncogenes by 2-3-fold compared with control. Topical application on the dorsal side of the skin with 1 mumol, 10 mumol, 20 mumol or 30 mumol of curcumin 30 min before TPA treatment inhibited the TPA-induced expression of these proto-oncogenes. Inhibition of expression of c-fos and c-jun was more pronounced than that of c-myc. A dose of 10 mumol of curcumin was found to inhibit 90% TPA-induced expression of c-fos and c-jun, and 60% of c-myc. These data strongly suggest that curcumin may inhibit skin cancer through the modulation of expression of these proto-oncogenes.