Phorbol 12-myristate 13-acetate (PMA) and opsonized zymosan (OZ)-stimulated superoxide-generating activity of neutrophils were measured by the cytochrome c reduction assay in 10 healthy young (21.4±0.4 yr) and 10 elderly (60.7±1.9 yr) women. Peripheral blood was collected three times, at the menstrual, ovulatory and luteal phases in the young women, and on largely the same days and intervals as those for the younger subjects in the elderly women. PMA-stimulated superoxide-generating activity of neutrophils did not change in the young and elderly groups. However, OZ-stimulated activity in the menstrual phase was significantly higher than in the ovulatory and luteal phases in the young women; no change was found in the elderly women. These results suggest that the superoxide-generating activity of neutrophils is transiently activated by physical and mental stress during the menstrual phase. This activation may occur due to a change in neutrophil receptors, signal transduction pathways and membrane fluidity without any increase of NADPH oxidase activity itself, which produces superoxide anions.