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Its source is in the remote western forests of the Pakaraima Mountains and its confluence with the Cuyuni River is near Bartica.
Next, the Mazaruni River flows past Oranapai Rapids, Kamakusa Landing, the mouth of Merume River, Banana Landing, Tiboku Rapids, the mouth of Equeribisi River, Issano Landing, the mouth of the Puruni River, Kaburi rapids, Marshal Falls, the last set of rapids, Itabali Landing, the mouth of the Cuyuni River, then, near the village of Bartica, finishes into the Essequibo River, the largest river of Guyana.