In the current study the authors have investigated whether human primary breast cancer specimens contain insulin-like growth factor-1 (IGF-1) receptors (IGF-1-R) or IGF-1-like activities. Simultaneously, epidermal growth factor (EGF) receptors (EGF-R) and cytosolic estrogen receptor (ER), progesterone receptor (PR), and EGF-like activity were determined. All tumors assayed contained a single class of specific iodine 125 (1251)-IGF-l binding sites (&: median 106, range 48-755 pM, n = 32) with limited capacity (Bmax: median 147, range 19-11,900 fmol/mg membrane protein). Seventy percent of 44 tumors (50% ER+, PR+), displayed specific 1251-EGF binding with a wide range of values (median 13, range 2-215 fmol/mg protein, n = 31). A positive relationship was apparent between the amount of IGF-1-R with ER and PR (Spearman; 2P < 0.02 and 2P < 0.01, respectively; n = 32), whereas for EGF-R a negative relationship was observed (for both 2P < 0.01; n == 44). All tumors contained endogeneous IGF-1-like and EGF-like activities as measured by radioreceptor assay on acid-ethanol extracted cytosols (median 15, range 3-131 ng/mg protein, n = 78 for IGF-1; and median 86, range 26-517 ng/mg protein, n = 142 for EGF). Tumor contents of IGF-1-like and EGF-like activities showed a negative relationship with ER (2P < 0.1 for IGF-1, n = 78; and 2P < 0.001 for EGF, n = 142), and with PR (2P < 0.05, n = 78; and 2P < 0.001, n = 142). No relationship was observed between the tumor contents of IGF-1-like and EGFlike activities. In conclusion, these data support the view that IGF-1 and EGF can act as autocrine or paracrine growth factors in human breast cancer.