Koko, the 46-year-old gorilla who mastered sign language, died in her sleep at a preserve in California's Santa Cruz mountains on Tuesday.
The western lowland gorilla was born at the San Francisco Zoo, and Dr. Francine Patterson began teaching the gorilla sign language that became part of a Stanford University project in 1974.
The Gorilla Foundation said Koko's capacity for language and empathy opened the minds and hearts of millions.
Koko appeared in many documentaries and twice in National Geographic. The gorilla's 1978 cover featured a photo that the animal had taken of herself in a mirror.
The foundation said it will honor Koko's legacy with a sign language application featuring Koko for the benefit of gorillas and children, as well as other projects.