Tamoxifen, an antiestrogen which competes for the estrogen receptor, modulates natural killer cell activity in vivo. Seventeen post-menopausal stage I breast cancer patients received tamoxifen for 1 month and a statistically significant increase in NK activity was demonstrated (P = 0.0005). There was a small incremental shift in the number of Leu-11b positive cells. These data demonstrate that tamoxifen functions as a biological response modifier.