Insulin, insulin-like growth factors (IGFs) I and II, and IGF binding proteins (IGFBPs) 1 and 3 have been implicated in breast cancer outcomes. We conducted a randomized controlled trial to determine the physiological effects of exercise training on changes in these biological markers in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control group (n = 28). The exercise group trained on cycle ergometers three times per week for 15 weeks. The control group did not train. End points included changes in fasting insulin, glucose, insulin resistance, IGF-I, IGF-II, IGFBP-1, IGFBP-3, and IGF-I:IGFBP-3 molar ratio between baseline and week 15. All of the statistical tests were two-sided (alpha = 0.05). Fifty-two participants completed the trial. The exercise group completed 44.3 of 45 (98.4%) prescribed exercise sessions. Baseline hormone concentrations did not differ between groups except that IGF-II was higher in the exercise group (P = 0.011). No significant differences between groups were observed for changes in fasting insulin (+6.3 pmol/liter; P = 0.941), glucose (+0.09 mmol/liter; P = 0.824), insulin resistance (+0.4; P = 0.247), IGF-II (-40.7 ng/ml; P = 0.101), or IGFBP-1 (+1.4 ng/ml; P = 0.774). However, significant differences between groups were observed for changes in IGF-I (-7.4 ng/ml; P = 0.045), IGFBP-3 (+180.5 ng/ml; P = 0.021), and IGF-I:IGFBP-3 molar ratio (-0.006; P = 0.017). Exercise training had significant physiological effects on IGF-I, IGFBP-3, and IGF-I:IGFBP-3 molar ratio in postmenopausal breast cancer survivors. The clinical implications of these findings remain to be defined.