This study reports the initial observation of the novel estrogen receptor, ER beta, in human subcutaneous adipose tissue. Human adipose tissue was obtained from various anatomic sites including the subcutaneous depots of lipectomy patients (healthy controls), and from subcutaneous abdominal and breast depots of lean and obese women with breast cancer. ER beta mRNA expression, determined by reverse transcription and polymerase chain reaction (RT-PCR), was present in each adipose tissue sample examined. Cloning and sequencing of the PCR product confirmed its identity as ER beta. Separation of adipose tissue into component fractions indicated that ER beta was expressed in both adipocytes and the stroma-vasculature. Primary culture of human preadipocytes indicated that ER beta mRNA was present only after differentiation to the adipocyte phenotype. This novel observation of ER beta mRNA indicates that this receptor subtype may have a role in ER-mediated responses in human adipose tissue.