Objective: Drugs addiction is considered a general major problem all over the world causing massive detrimental effects for the addict, communities and governments. The study was designed to assess the dependency impact of concurrent brown heroin and Tramadol administration on reproduction in rats. Material and methods: Sixty adult male albino rats were divided into untreated control (I), vehicles groups citric acid (II), saline (III), brown heroin (IV), tramadol (V) and concurrent brown heroin and tramadol (VI) groups. The animals were treated daily for forty days by oral (saline and tramadol) and intra-peritoneal (citric acid and heroin) routes. The body weights, the reproductive hormonal assay (luteinizing hormone LH, follicle stimulating hormone FSH, free Testosterone, Estradiol E2 and prolactin PRL) and the hormones related gene expression (brain FSH-B gene, LH-B gene and testicular cytochrome 19 gene CYP-19) were evaluated. The histopathological changes of the brain and testis were demonstrated. Results: The brown heroin, tramadol and the concurrent brown heroin and tramadol administration reduced the rats' body weight, serum LH, FSH and Testosterone and increased the serum E2 and PRL levels. Moreover, both heroin and tramadol produced down regulation of brain LH-B and FSH-B with up regulation of testicular CYP-19 genes expression and induced histopathological alterations in both of the brain and testicular structures. Conclusion: The concurrent brown heroin and tramadol dependency affect the reproductive axis and impaired fertility in adult male albino rats via altering the circulating reproductive hormones and its related genes expression, moreover, affecting the histology of the brain and testis. Recommendation: Health education for the purpose of increasing public awareness regarding hazards of tramadol and heroin addiction, periodic urine screening for early detection and proper management which could be done for university students, employee in different community services….etc