Recently hormone - dependent mammary carcinoma cell lines were shown to exhibit in vitro significantly lower protein kinase C (PKC) activities and epidermal growth factor receptor (EGF-R) as compared to hormone - independent cell lines. Measurements of EGF-R levels in primary human breast cancer biopsies were determined by [125I]-EGF binding. The EGF binding correlated inversely with the estrogen (ER) (p less than 0.001), progesterone receptor (PR) (p less than 0.005) contents and with the age of the patients. In contrast, the amounts of PKC, determined by phorbol ester binding, correlated inversely only with the PR (p less than 0.001), but not with the ER (p = 0.065). There was, however, a significant inverse correlation (p less than 0.05) between phorbol ester binding and ER levels if ER positive biopsies but with a PR negative value (i.e. with a non functional estrogen receptor) were excluded from statistical analysis. These data suggest an inverse relationship between the EGF-R or the phorbol ester receptor and the steroid receptor system in human breast cancer.