OBJECTIVE To identify the alpha1-adrenoceptor subtypes present in the human urethra, by comparing the affinity of prazosin for alpha1-adrenoceptors in the rabbit, dog and human prostatic urethra, and in the dog and human prostate. METHODS The study comprised samples of human prostate and prostatic urethra, obtained by open prostatectomy of patients with benign prostatic hyperplasia, and of the proximal urethra and prostate from male Beagle dogs and rabbits. Specimens were homogenized, filtered and pelleted by centrifugation. Nonspecific binding was determined in the presence of 1 mmol/L prazosin when assessing [3H]YM-617 (tamsulosin) binding, and 10 mmol/L phentolamine when assessing [3H]prazosin binding. Specific binding was defined as the difference between total binding and nonspecific binding. RESULTS The dissociation constant for [3H]prazosin in the human prostate (0.088 nmol/L) was less than that in the rabbit urethra (0.299 nmol/L), dog urethra (0.604 nmol/L), dog prostate (0.482 nmol/L) and human urethra (0.254 nmol/L). The affinity of prazosin was also investigated by determining the potency of the inhibition of [3H]YM-617 binding. The affinity of prazosin for alpha1-adrenoceptors in the human urethra (Ki, 2.5 nmol/L) was lower than its affinity for alpha1-adrenoceptors in the human prostate (Ki, 0.25 nmol/L) and all of the cloned subtypes (Ki, 0.26-0.44 nmol/L). CONCLUSIONS The alpha1L-adrenoceptor subtype is more prominent in the human, rabbit and dog urethra and dog prostate than in the human prostate.