Its source is in the Guainía Department of Colombia, where it is known as the Isana River.

From its source, it flows mostly east until it reaches the border between Colombia and Brazil, where the river forms a small part of the boundary between the two countries.

From the border, it flows mostly southeast through Amazonas state until it joins the Rio Negro at Missão Boa Vista.

In Brazil, the river flows through the Alto Rio Negro Indigenous Territory, which was created in 1998.

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