Estrogen receptor (ER) status is an accepted prognostic indicator for breast cancer when measured by either the biochemical or immunohistochemical (ERICA) methods. Moreover, ERICA was found to be a better predictor of survival in human breast cancer than the biochemical assay for ER. The antibody to Ki67 recognizes the growth fraction of proliferating cells. We examined 100 primary breast cancers to investigate the relationship between ER status as measured by ERICA and Ki67 reactivity. Of the 56 ERICA positive cases, 47 (84%) were Ki67 negative whereas 30 of the 44 ERICA negative tumors were Ki67 positive (68%). There was evidence of a significant inverse relationship between ERICA and the growth fraction (77% of cases, p less than 0.001). In addition, a cluster of ERICA-positive Ki67-positive tumors that were larger and occurred in older patients was identified as a subset that might require aggressive therapy. Our results suggest that Ki67 may be an important additional criterion for predicting the biological behaviour of breast cancers.