Cow's Skull: Red, White, and Blue prominently displays the three colors of the American flag. Painted at a time when American artists, musicians, and writers were interested in identifying a uniquely American style and subject matter for their work, O'Keeffe offered a dissenting opinion about what images could best symbolize America. Rather than paying homage to the lush agricultural landscape as the Regionalist painters did, or uncovering urban problems like the American Scene painters, she used a weathered cow's skull to represent the enduring spirit of America. Although she made it as a joke on the concept of the "Great American Painting," the picture is a quintessential icon of the American West.

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