Introduction and objective There are dual reasons for the emergence of BPH: an increase in smooth muscle tone as well as an increase in the size and growth of the prostate gland. Smooth muscle tone is treated using α1 adrenoreceptor antagonists to reduce urethral obstruction by relaxing contractile tissue of the prostate gland and perhaps the urethral muscle as well. However, relatively little is known about smooth muscle function in this organ and the mechanism and effectiveness of α adrenergic drugs and how they directly regulate contractility prostate gland smooth muscle itself, is equivocal. Hence the aim of the current study was to investigate the direct effect of clinically used α1 adrenoreceptor antagonists on prostate contractility in specimens from males with BPH, or prostate enlargement. Methods Transition zone tissue (10mm X 15mm) from the prostate gland was obtained from consenting patients undergoing radical prostatectomy. These patients are diagnosed with BPH (volume >70cc and pathology) and have low to moderate grade prostate cancer; they will have had radical prostatectomy to surgically treat both conditions. TZ tissue was placed into ice-cold RPMI medium supplemented with 5% fetal calf serum and antibiotics (penicillin at 300 units/ml, streptomycin at 300 μg/ml and amphotericin at 1 μg/ml). Contractile recordings were made from prostatic preparations (3mm X 10mm) using standard tension recording techniques as we have previously described. Results All specimens contracted spontaneously at a frequency of 2.2 +/- 0.4 contractions per minute; the duration of each contraction was >12 seconds (n=18). The basal tension was 4.4 +/- 0.4 mN and the amplitude (normalised for tissue weight) was 0.20 +/- 0.03 N/g. Epidemiological data show that the incidence of BPH is age related and rises in men as they become older. Preliminary data show an age related change in men from 50 to >60 yo such that there is an increase in amplitude (from 0.13 +/- 0.05 N/g to 0.21 +/- 0.03 N/g) and frequency (from 1.4 +/- 0.2 min-1 to 2.5 +/- 0.6 min-1) of the spontaneous smooth muscle contractions with age. Tamsulosin (0.3nM) and prazosin (1.0μM) failed to completely block spontaneous contractility in the TZ of the human prostate gland but appeared to reduce the amplitude of the spontaneous contractions to ~70 % of control (both n=4; p<0.05 Student’s paired t test). In addition, there appeared to be variation in the response by individual patients. Conclusion The results in human tissues fully substantiate our work with guinea-pig tissues and consistently provide explanation for the aetiology of the increase in smooth muscle tone observed in patients with BPH. The variability in the response to α1 adrenoreceptor antagonists foreshadows the need to consider individual vs group responses to current pharmacotherapy.