Alkylating agents, which are metabolized by glutathione S-transferase (GST), have an important role in the etiology of cancer by forming mutagenic DNA adducts. Previous studies have shown that DNA repair protein, O-6-methylguanine DNA methyltransferase, repairs these mutagenic DNA adducts and its activity is correlated with the resistance of human tumors to alkylating agent-based anticancer drugs. However, little is known about GST and O-6-methylguanine DNA methyltransferase activities in patients with thyroid cancer in vivo. We measured the activities of GST and O-6-methylguanine DNA methyltransferase in the leukocytes from patients with papillary thyroid carcinoma and healthy controls. The GST activity was significantly higher in men than in women, and it was negative correlated with age in men whereas it was unchanged in women in the control group. Both GST and O-6-methylguanine DNA methyltransferase activities were significantly increased in the patient group. There were no age and sex-related changes in the O-6-methylguanine DNA methyltransferase activity in both the control and patient groups. These results suggest that leukocyte GST and O-6-methylguanine DNA methyltransferase activities were increased with thyroid cancer. This may be related to the resistance to chemotherapy exhibited by patients with thyroid cancer.