The behavior of progesterone receptor (PR) values over time in human breast cancer during tamoxifen treatment was studied. Of 97 patients with operable breast cancer, 24 were preoperatively treated with tamoxifen (20 mg twice daily) for 3 days (TAM 3-day), 22 were treated for 7 days (TAM 7-day), 21 for 14 days (TAM 14-day), and 30 received no treatment (control group). Surgically removed breast tumors were assayed for the progesterone receptor by the dextran-coated charcoal method. The PR values (fmol/mg DNA) (mean +/- standard error [SE]) of PR-positive tumors in the control, TAM-3, TAM-7, and TAM-14 day groups were 571 +/- 176, 1699 +/- 408 (P less than 0.01), 1675 +/- 463 (P less than 0.05), and 686 +/- 191, respectively. There was a 4.6-fold increase in the mean PR value in postmenopausal patients and a two-fold increase in premenopausal patients after TAM treatment for 3 and 7 days. We concluded that PR induction provoked by TAM reached a peak on day 3, continuing at this level until day 7. A longer treatment (14 days) with TAM appears to abolish the PR inducing activity, probably because of, first, estrogenic and, later, the antiestrogenic effects of TAM.