Stromal nodules from benign prostatic hyperplasia (BPH; n = 375 from autopsy, n = 100 from biopsy specimens) were investigated with regard to cytoskeletal components, topography, vascularization, leukocytic infiltrates,and proliferative activity. Methods: The nature of stromal nodules was studied by histopathology and immunohistochemistry, using antibodies against α-actin, desmin, myosin, vimentin, BMA-120, factor VIII, CD3, CD4,CD20, CD34, CD45RO, CD68, PCNA, and MiB1. Results: The findings lead to an extended classification of stromal nodules in BPH: immature mesenchymal(IM; 8.8%), fibroblastic (FB; 65.2), fibromuscular (FM; 21.6), and smooth muscular (SM; 4.4%). The different types occurred in all age decades in a similar distribution (FB > FM > IM > SM). Topographical studies (modified zonal subdivision of McNeal) revealed stromal nodules predominantly in the transitional zone (n = 286), less in the central zone (n = 78), occasionally in the peripheral zone (n = 11), and predominantly in the periurethral (n = 287) and less in the intermediate (n = 84) and subcapsular (n = 4) regions. The different types of nodules presented a distinct vascular pattern. FB, FM, and SM nodules showed significantly increased diffuse infiltrates of T lymphocytes -mainly T helper cells (mean 73%) - and an increase of B lymphocytes. Proliferative activity in the nodules was not observed. Stromal nodules were not observed in normal nonhyperplastic prostates; they only occurred in combination with hyperplastic nodular glandular proliferates. Conclusions: The findings are suggestive of a maturational sequence of stromal nodules in BPH and of a possible significance of immunocompetent cells in the development of stromal nodules and further suggest that both stroma and epithelium of the prostate respond with nodular hyperplasia to the stimulus, which causes BPH.