The qualitative and quantitative relationships between cytoplasmic estrogen receptors (ERC), total nuclear estrogen receptors (ERN), and cytoplasmic progesterone receptors (PGR) in 74 primary and 23 metastatic human breast cancer tissues were studied. A positive correlation between the age of th patients and the receptor concentration was found only for ERC. Although ERN and PGR were more frequent in tumors with a higher level of ERC, there was no significant correlation between concentrations of either ERN or PGR and ERC. However, PGR were more frequent in ERN-positive than in ERN-negative tumors, irrespective of the presence of ERC. There was also a highly significant correlation between PGR and ERN concentrations. These findings support the assumption that induction of PGR by estrogen in human breast cancer is mediated by a mechanism involving nuclear receptors. Therefore, the ERN assay might increase the validity of steroid receptor determination for prediction of hormonal sensitivity of human breast cancer.