The protective effect of curcumin, a potent inducer of heat shock protein (Hsp) 70, against the acute toxicity produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in vivo in C57BL/6J mice. Curcumin reduced the loss of body weight gain produced by TCDD regardless of having no effect on hepatomegaly and thymic atrophy. Hsp70.1 mRNA levels in liver and intestine were unaffected or tended to be reduced by TCDD and/or curcumin treatment. Curcumin also had no effect on the induction of hepatic ethoxyresorufin O-deethylase activity by TCDD. These data suggest that curcumin exhibits a protective effect against some forms of dioxin toxicity by a mechanism(s) distinct from the increase in hepatic and intestinal Hsp70 and inhibition of arylhydrocarbon receptor activation.