The contribution of a cellular immune response to tissue destruction in sclerosing lymphocytic lobulitis of the breast is not well understood. In this study, comparison of one case with two age matched control cases showed an increased frequency of activated perforin mRNA expressing cells at the site of tissue destruction in lobulitis. Along with the detection of tumour necrosis factor alpha (TNF alpha) mRNA expressing cells in the infiltrates, the striking association of perforin expressing activated cytotoxic cells with remaining gland parenchyma and the high level of perforin mRNA suggests activation of cytotoxic cells in situ. These findings are evidence that cell mediated cytotoxicity plays a significant role in the destruction of mammary gland tissue in sclerosing lymphocytic lobulitis.