Curcumin, a yellow pigment of turmeric (Curcuma longa), is a commonly used spice and a coloring agent in foods, drugs, and cosmetics. Curcumin is known to possess chemopreventive properties in various animal tumor models. In the present study the effect of curcumin on the development of altered hepatic foci (AHF), by using a medium term liver bioassay, has been evaluated. AHF were analyzed by quantitative stereology using the Leica Qwin Image Analysis system from frozen liver sections stained for gamma-glutamyl transferase, adenosine triphosphatase, glucose-6-phosphatase, alkaline phosphatase, and placental isozyme of glutathione S-transferase. A significant protection on diethylnitrosamine (DEN) initiated and 2-acetylaminofluorene (AAF) promoted AHF by curcumin was observed on these biological markers. The curcumin administration was found to restore the normal levels of the enzymes glutathione S-transferase and gamma-glutamyl transferase in rat liver following DEN-AAF exposure. Similarly, a significant protection was provided by curcumin in the enzyme-deficient foci for the adenosine triphosphatase-, alkaline phosphatase-, and glucose-6-phosphatase-treated groups in comparison to the DEN-AAF-treated group. These results show that curcumin can effectively suppress the DEN-induced development of AHF in rat liver.