The effect of Xiao-chai-hu-tang (TJ-9) on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given normal chow pellets containing 0.5% or 1.0% TJ-9 until the end of the experiment, and drinking water containing NNM for 8 weeks. Pre-neoplastic and neoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically. In Week 15, quantitative histological analysis showed that prolonged treatment with 0.5% TJ-9 significantly reduced the number and volume of GGT-positive and GST-P-positive hepatic lesions. Treatment with 1.0% TJ-9 inhibited the development of GGT-positive and GST-P-positive lesions, but was less effective than 0.5% TJ-9. Administration of 0.5% TJ-9 also caused a significant increase in the proportion of helper T lymphocytes and a significant decrease in the labeling index of pre-neoplastic lesions. These findings indicate that TJ-9 inhibits the development of hepatic foci.