Agricultural and industry discharge water are considered the most dangerous water pollution sources to the River Nile at Greater Cairo. Consequently, the chemical analysis of the water in the River Nile at selected stations as the determination of some heavy metals and pesticides have a great importance to people health. Therefore, the aim of this work was to assess if the changes of the River Nile at Greater Cairo water and fish (Oreochromis niloticus, Tilapia zillii and Clarias gariepinus). The selected stations were before El-Hawamdyia, El-Hawamdyia, after El-Hawamdyia, Shoubra El-Khima, El-Warrak and El-Kanater El-Khyria. The study included water quality, heavy metals (water, sediment and fish), inorganic anions (water, sediment and fish), pesticides distribution (water, sediment and fish) and water microbiology during 2014-2015. Pesticide residues (water, sediment and fish) showed that, chlorpyrifos had most detected amount followed by dicofol. Microbiological studies showed that there were some contaminations distributed at all sides with coliform, Escherichia coli pathogenic strains and Faecal streptococci. Hoosier Riverwatch Water Quality Index also were done.