Curcumin is a dietary pigment responsible for the yellow color of curry. It is a potent inhibitor of tumor promotion induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse skin. When mouse fibroblast cells (NIH 3T3) were treated with TPA alone, protein kinase C (PKC) translocated from the cytosolic fraction to the particulate fraction. Treatment with 15 or 20 microns curcumin for 15 min inhibited TPA-induced PKC activity in particulate fraction by 26 or 60% and did not affect the level of PKC protein. Curcumin also inhibited PKC activity in both cytosolic and particulate fractions in vitro by competing with phosphatidylserine. However, the inhibitory effect of curcumin was reduced after preincubation with the thiol compounds. These findings suggest that the suppression of PKC activity may contribute to the molecular mechanism of inhibition of TPA-induced tumor promotion by curcumin.