Natural killer (NK) cells are important in surveillance against malignant cells. The activity of NK cells can be modulated by naturally occurring mediators; interferon, interleukin-2, and hormones. Low-dose aminoglutethimide (Ag 250 mg/day) inhibits the peripheral aromatization of androstenedione hence decreasing circulating estrogens. Of ten patients treated, seven were evaluable. There was a statistically significant increase in NK activity (P = 0.0025) following the administration of Ag. There was no consistent shift in NK cell number (Leu-11b positive cells). In vitro Ag did not alter NK activity whereas 17-beta-estradiol did. These data are consistent with an indirect effect of Ag on NK activity. Hence in vivo Ag which causes a reduction in serum estrogens in postmenopausal patients, also induces an increase in NK activity.