Introduction: Azathioprine and Methotrexate are both used in the treatment of cancer; and are classified as cytotoxic drugs with reported adverse effects such as oxidative damage to the DNA/RNA, the testes and sperm cells. This study, therefore, tested the hypothesis that Azathioprine and Methotrexate administrations impair the morphology and functions of the testes in adult male wistar rats. Methods: Azathioprine (50-150mg per day) and Methotrexate (2.5mg per week) are used in the treatment of cancer in adult Man. We tested the hypothesis that Azathioprine and Methotrexate impair the morphology and functions of testes in rats. Forty adult male wistar rats (150-230g) were employed in the study: Control Group I received physiological saline while Experimental Groups II - V received oral administrations of 5mg/kg/bodyweight of Azathioprine per day, 15mg/kg/bodyweight of Azathioprine per day, 8mg/kg/bodyweight of Methotrexate per week and 20mg/kg/bodyweight of Methotrexate per week respectively for 35 days. Results: Histological examinations of the testes of rats of Groups II – V showed dose-dependent morphological anomalies such as fewer collagen fibers of connective tissues, disrupted seminiferous tubules and scanty spermatozoa when compared to rats of Group I. Statistical analyses showed dose-dependent elevated levels (P≤0.05) of superoxide dismutase and malondialdehyde in testes homogenates of rats of Groups II – V when compared to rats of Group I. This implied increased oxidative stress in rats of Groups II – V. Evaluations of Follicle Stimulating Hormone and Testosterone showed dose-dependent significantly elevated levels (P≤0.05) in rats of Groups II – V when compared to rats of Group I. Conclusions: Our findings are consistent with the stated hypothesis.