Estrogens affect longitudinal bone growth through their action on endochondral bone formation. Two estrogen receptors are known, the classical estrogen receptor-alpha (ER-alpha), newly demonstrated in human growth plate cartilage, and a recently cloned estrogen receptor-beta (ER-beta). The present study aimed to localize a possible expression of ER-beta protein in human growth plates. Tissue samples were obtained from tibial and femoral growth plates in four female pubertal patients undergoing epiphyseal surgery. Immunohistochemistry, using two different ER-beta-specific antibodies, demonstrated positive staining ER-beta in hypertrophic epiphyseal chondrocytes from all patients. No staining was noted in resting or proliferative chondrocytes. These data suggest that in addition to ER-alpha, human epiphyseal chondrocytes also express ER-beta. The physiological role of ER-beta in the regulation of longitudinal bone growth in humans remains to be elucidated.