BACKGROUND. Despite good results of high-energy transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia, it is still difficult to predict the response to treatment on an individual basis. Besides clinical baseline parameters, intrinsic histological parameters are suggested to play a role in the response variance after TUMT. In this study we analyzed histological parameters (vessel density and epithelium-stroma (E/S) ratio) in patients who were selected for high-energy TUMT and related these parameters to clinical outcome. METHODS. We treated 42 patients with high-energy TUMT, who prior to treatment agreed upon ultrasonographic investigation of the prostate in combination with biopsies of the peripheral and transitional zones of the prostate. For all separate biopsy locations, the histological stained prostate slides were morphometrically quantified with computer assistance and analyzed for E/S ratio and vessel density. Response to treatment was measured by using standardized response evaluation criteria and was correlated with histological outcome. RESULTS. The E/S ratio in the inner gland biopsies tended to be higher in the good response group compared to the very poor responders. Furthermore, a clear trend was seen towards a lower vessel density in good responders. Large prostates and prostates with a high E/S ratio responded well to the high-energy thermotherapy. CONCLUSIONS. Histopathological parameters of the prostate tend to be moderately predictive for clinical response in this research population. Poor responders appeared to have a somewhat higher vessel density in all prostate biopsy sides, and there was also a trend towards a lower E/S ratio in these patients.