Consideration of existing data regarding clinical and biochemical risk factors for the development of breast cancer leads to the hypothesis that enhanced insulin-like growth factor 1 (IGF-1) activity plays a significant role in the development of this disease. Abnormal IGF-1 activity may be related to events occurring prenatally, during puberty, or during adult life. Insulin resistance, a common feature in populations characterized by high caloric intake, may result in the amplification of IGF-1 action at the tissue level by altering serum concentrations of IGF-1 binding proteins. Several approaches toward testing the hypothesis are proposed, and potential opportunities for clinical application are described. © 1995 Wiley-Liss, Inc.