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The use of phosphodiesterase-5 inhibitors has become the first-line treatment of erectile dysfunction nowadays. The daily application of tadalafil has become a line of treatment of other diseases such as pulmonary hypertension and cardiomyopathy. This study aimed at exploring whether the chronic use of tadalafil has an adverse effect on the testes and semen of old albino rats. Sixty male albino rats were divided into three groups. Group 1: given 2 ml saline orally for 90 days. Group 2: received tadalafil orally (1.8 mg kg(-1) day(-1) for 3 months equivalent to 20 mg day(-1) for 3 months as in human dose) and Group 3: received tadalafil orally (1.8 mg kg(-1) day(-1) for 6 months equivalent to 20 mg day(-1) for 6 months as in human dose). Animals were observed daily for signs of toxicity and mortality. Body weight and food consumption were recorded once a week. After sacrificing the animals, gross examination of the testes was performed in situ and then the epididymis was processed for the evaluation of sperm parameters and testes with other organs relative weight was calculated. Testicular histopathological examination was performed to evaluate microscopic changes in the seminiferous tubules. The mean testicular weight was significantly lower in animals of Group 3, and no significant changes were observed in Group 2. Sperm count showed a significant time-dependent decrease. Sperm motility decreased significantly in both groups with higher effect in Group 3. Incidence of abnormal forms increased in both groups (about 5 and 7 times in Group 2 and 3 respectively). Histological examination revealed mild changes in Group 2 and moderate changes in Group 3 in the form of loosely packed connective stroma around seminiferous tubules, reduction in number of spermatogenic cells with sloughing of many spermatocytes within the lumen of some tubules. Large vacuoles appeared in the tubules which contained a fewer number of sperm. Sperm bundles were degenerated in most tubules and completely absent in others. It is concluded that chronic daily use of tadalafil produces detrimental effects on the structure and function of the testes of old male albino rats which are duration dependent., (© 2011 Blackwell Verlag GmbH.)