The interactions between protein kinase C (PKC) and the steroid hormone estradiol or its receptor (ER) are reviewed. Estradiol upregulates PKC both in vitro and in vivo in the ovary, the anterior pituitary and in mammary tissue of several mammalian species. The antiestrogen tamoxifen inhibits PKC. Activation of PKC leads to a marked decrease of ER protein and ERmRNA in human breast cancer cells and some other cell lines. Inhibition or down-regulation of PKC enhances ER binding. These results indicate that there are links between the PKC signal transduction pathway and the steroid receptor family. Further studies are needed to clarify the role of PKC isoforms in normal and cancerous tissues which are known to be influenced by estradiol.