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The Cuyuni River is a South American river and a tributary of the Essequibo River. It rises in the Guiana Highlands of Venezuela where it descends northward to El Dorado, and turns eastward to meander through the tropical rain forests of Guyana. It finally turns southeastward, flowing to its confluence with the Mazaruni River. The Cuyuni River marks the limit of the disputed territory of Guayana Esequiba for approximately 100 kilometres (62 mi).
In 1681, an island in the mouth of the Cuyuni River was cleared and planted with cassava for the use of the Dutch garrison. By 1694, a new plantation on the Cuyuni River above the fort was established. By 1703 a post was established on the Pariacot Savannah, in the upper Cuyuni.
In January 2, 1895 the "Incident of the Cuyuni river" names by the general Domingo Antonio Sifontes, was an armed confrontation between Venezuelans and British occurred in the region of River by the territorial dispute that had Venezuela with the British Guyana, in which by direction of Sifontes the Venezuelans left winners.
At dawn, British police men led by "Inspector Barnes" of England, took an unoccupied military station of Venezuelan nationality, located on the left coast of the river, in which the men of Barnes hoisted the British flag in Venezuelan lands during the day.
Facing this fact, the captain Andrés Avelino Domínguez, second to the control of Sifontes, was sent to recover the settlement. The result was the withdrawal of the British and the capture of Barnes and his men, who were taken to the General Police Station, which increased tensions between the two countries amid an internal crisis in Venezuela. 
The Kamaria hydroelectric power site is located on the Cuyuni River.
The river is a source of alluvial gold.
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