A small increase in the risk of breast cancer has been reported after long term use of combined estrogen-progestagen treatment. Free oxygen radicals and antioxidants such as glutathione are involved in the regulation of proliferation and apoptosis and thereby in carcinogenesis. To study whether the glutathione levels are sex hormone dependent, we used the microdialysis technique to measure the in vivo concentrations of glutathione in breast tissue and sc fat during the menstrual cycle. Six healthy women (23-32 yr old) were investigated early in the follicular phase and the midluteal phase. Two 60-min fractions each were collected by microdialysis of periumbilical fat and breast tissue, respectively. The samples were stored at -70 C and analyzed by high performance liquid chromatography. Glutathione concentrations increased in the midluteal phase compared to those in the follicular phase in both adipose tissue and breast tissue (P < 0.05). The variability of glutathione levels during the menstrual cycle, with higher levels late in the menstrual cycle, indicates that the antioxidant system could be sex hormone dependent. This may be of importance in breast cancer development.