To elucidate the physiologic and pathologic roles of androgen receptor (AR) and co-regulators in human testes with obstructive azoospermia or nonobstructive azoospermia.Prospective laboratory and clinical study.Infertility clinic at Chang Gung Memorial Hospital.Twenty-seven men with obstructive azoospermia and 24 men with nonobstructive azoospermia.None.Expression of AR and AR co-regulators was determined in testicular specimens and were analyzed using reverse transcription polymerase chain reaction (PCR) and immunohistochemical staining techniques.Most of the AR co-regulators were expressed at similar levels in specimens obtained from men with nonobstructive and obstructive azoospermia. However, the levels of expression of ARA54 mRNA were significantly lower and ARA55 mRNA was significantly higher in specimens from men with nonobstructive than obstructive azoospermia. In specimens from men with obstructive and nonobstructive azoospermia, AR immunostaining was detected in Sertoli, Leydig, and peritubular myoid cells. ARA55 immunostaining was detected in peritubular myoid and endothelial cells of blood vessels. Interestingly, nuclear ARA54 immunostaining was detected in the late stage germ cells of specimens from men with obstructive azoospermia but in the somatic cells of specimens from men with nonobstructive azoospermia.These results demonstrated that the decreased expression of ARA54 and increased expression of ARA55 is a feature of nonobstructive azoospermia. In addition, the differential localization of ARA54 may play an important role in testicular development and spermatogenesis in humans.