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Background. Insulin‐like growth factor I (IGF‐I) is a potent mitogen for breast cancer cells. The majority of IGF‐I in plasma is bound to IGF binding proteins (IGFBPs), which modulate the biologic effects of IGF‐I. Methods. Plasma concentrations of IGF‐I, IGFBP‐I, and IGFBP‐3 were compared between 40 postmenopausal breast cancer patients receiving long term tamoxifen therapy and 39 breast cancer patients receiving no hormonal treatment. In an additional group of seven patients, serum levels of IGF‐I and IGFBP‐I were determined before and during treatment at 6 and 12 months. Results. The tamoxifen and. the control groups did not differ with respect to age, parity, age at menopause, or body mass index. There were no significant differences in the mean concentrations (± standard error of the mean) of IGF‐I (10.0 ± 0.4 nmol/l and 11.2 ± 0.5 nmol/l, respectively) and IGFBP‐3 (3.2 ± 0.1 mg/l and 3.1 ± 0.1 mg/l, respectively), whereas the mean value of IGFBP‐1 was significantly higher in the tamoxifen group (G. O 05 0.6 pg/l versus 2.8 5 0.3 pg/L, P = 0.0001). No significant differences were found in the insulin levels. During the treatment, concentrations of IGF‐I decreased at 6 months and began increasing at 12 months. IGFBP‐1 levels increased at 6 months and remained elevated at 12 months. Conclusions. The tamoxifen‐induced increase in IGFBP‐1 plasma levels may be an important mechanism modulating IGF‐I action at the tissue level.