In a previous report, we demonstrated intense lymphocytic infiltration of all benign prostatic hypertrophy (BPH) tissues analyzed in conjunction with HLA-DR expression on normally MHC-class-II-negative prostate epithelial cells. The composition of these infiltrates (70 to 80% CD3+ T-cells, but no granulocytes) resembles the situation seen in immune responses against altered self or self rather than against foreign antigens (infection). In the present study, phenotypic and functional immunoassays were used in order to investigate whether T-cells in BPH are indeed activated, and whether this activation is systemic or restricted locally to the prostate. Analysis of T-cell activation marker expression and proliferation requirements provided substantial evidence that these infiltrating lymphocytes, in contrast to their peripheral counterparts, are chronically activated. Since local accumulation of activated lymphocytes can cause tissue destruction, high concentrations of cytokines, and consequently tissue rebuilding, this process might contribute to the pathogenesis of BPH.