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Many autoimmune diseases including rheumatoid arthritis (RA), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) occur much more frequently in women than in men. There is much evidence that oestrogen is the major cause of this gender difference. Interestingly, oestrogen relieves the symptoms of RA and SS but it exacerbates SLE. This contradictory effect of oestrogen on autoimmune diseases is not well understood. Most of the effects of oestrogen are mediated by two receptors: oestrogen receptor α and β (ERα and ERβ). To determine whether these contradictory effects of oestrogen relate to the involvement of distinct effects of the two ERs, we investigated expression of ERα and ERβ in human secondary lymphoid tissues. We observed that, in tonsils, ERβ is expressed in lymphocytes of germinal centres (GC) and the follicular mantle zone as well as in granulocytes, while ERα is expressed only in activated germinal centres but not in the follicular zone. ERβ is the predominant ER in human leucocytes from peripheral blood, spleen and in leucocytes infiltrating cancers in both males and females. In addition, in different human lymphoma cell lines including Hodgkin lymphoma, Burkitt lymphoma, and multiple myeloma, ERβ is abundant while ERα is not detectable. Our results indicate that ERβ is the predominant type of ER in mature lymphocytes. We suggest that ERα and ERβ have distinct roles in secondary lymphoid tissues and that further studies with ERβ-specific agonists will help to elucidate the role of ERβ in these tissues. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.