The prostatic epithelium has generally been described as consisting of three separate cell types--secretory, luminal, basal and endocrine-paracrine (EP) cells--that differ by their morphological features, functions and hormonal regulation. Compared with the gastrointestinal tract and other self-renewing tissue, little is known about differentiating and proliferative processes in the normal and hyperplastic human prostate. In the present report, we propose a stem cell model for the organization of the prostatic epithelium that may explain normal and abnormal growth in the human prostate. This model is based on recent data indicating that 1. the three basic cell types encountered in the prostatic epithelium are linked in precursor-progeny relationship as documented by the existence of intermediate phenotypes, 2. the basal cell layer represents the proliferative compartment in normal and hyperplastic conditions, 3. EP-cell types do not proliferate and lack the nuclear androgen receptor (AR), 4. basal cells may be potentially androgen-responsive as documented by the presence of AR, 5. formation of basement membrane (BM) deposits is crucial in the development of the invasive phenotype. In this model, a small stem cell population located in the basal cell layer gives rise to all epithelial cell lineages encountered in the normal, hyperplastic and neoplastic prostate. The differentiating process from basal cells to secretory luminal cells via intermediate phenotypes is induced by circulating androgens, and largely depends on the presence of responsive target cells in the basal cell layer. Accordingly, the abnormal growth of the secretory epithelium in benign prostatic hyperplasia may be related to an increase in the total number of androgen-responsive basal cells.(ABSTRACT TRUNCATED AT 250 WORDS)