Cells possess within their epigenetic repertoire the ability to undergo an active process of cellular suicide, ie apoptosis. This represents the physiologically relevant mode of cell death that proceeds via an energy-dependent cascade of biochemical and morphological changes which result in the death and elimination of the cell. 1 In the normal prostate, the rate of cell proliferation is balanced by an equal rate of cell death, so homeostasis of the gland is maintained. 1 In both clinical conditions associated with the pathogenesis of prostatic disease in the aging male, prostate cancer and benign prostate hypertrophy (BPH), there is an imbalance in the growth equation in favour of cell proliferation, thus resulting in an increased cell number and abnormal prostatic growth. 2,3 Targeting apoptosis for controlling prostatic growth equilibrium, emerges as a novel therapeutic approach for the effective treatment of prostate cancer (androgen-dependent and androgen-independent tumours), and long-term medical management of BPH. 4 Benign prostatic hyperplasia (BPH), histologically represents a spectrum of hyperplasia between the stroma and glandular epithelial components of the aging prostate. The therapeutic bene®t of a1-adrenoceptor antagonists in BPH is believed to be due to a change in the peri-urethral tone of the prostate via an action on a1-adrenoceptors, which are abundant in the gland. In a recent retrospective study, tissue from BPH patients treated with the a1-adrenoceptor antagonists, terazosin or doxazosin were subjected to in situ analysis of apoptosis and cell proliferation. 5,6 Our results revealed that both doxazosin and terazosin resulted in a signi®cant increase of the apoptotic index in both stroma smooth muscle and glandular epithelial cells of BPH prostate, while it had no effect on the proliferative capacity of the respective cell populations. This effect was time-dependent, reaching a maximum at 4 ± 6 months of treatment and returning to near baseline after longer treatment periods. 5,6 Signi®-cantly enough, there was a correlation between enhanced apoptosis with both reduction in stroma smooth muscle a-actin and improvement of BPH symptoms. 5,6 Thus the clinically used a1-adrenoceptor antagonists doxazosin and terazosin induce prostate apoptosis over the normal therapeutic dose for BPH treatment. This evidence supports the concept that apoptosis-mediated stroma smooth muscle-regression is a potential mechanism underlying the therapeutic response to a1-blockade and contributing to the overall clinical pro®le of doxazosin and terazosin, probably via adrenoceptor-independent actions. Further immunohistochemical analysis revealed an upregulation of expression of TGF-b, a physiological regulator of prostate apoptosis, among both cellular components (stroma and epithelium) of BPH prostates following a1-blockade. These ®ndings suggest the potential involvement of TGF-b in the apoptotic response of prostate cells to a1-adrenoceptor antagonists.More recent studies demonstrated that doxazosin and terazos...