This activity provides an introduction to natural selection and the role of genetic variation by asking students to analyze illustrations of rock pocket mouse populations (dark/light fur) on different color substrates in the Sonoran Desert (light/dark) over time. Based on this evidence, and what they learn about variation and natural selection in the accompanying short film, students use this evidence to explain the change in the rock pocket mouse populations on the lava flow (dark substrate) over time. This is one of several classroom activities, focusing on related topics and varying in complexity, built around the short film. This ten minute film shows adaptive changes in rock pocket mouse populations, demonstrating the process of natural selection and can be accessed at http://www.hhmi.org/biointeractive/making-fittest-natural-selection-and-adaptation. The film is also available as an interactive video with embedded questions, which test students’ understanding as they watch the film. That version can be accessed at http://www.hhmi.org/biointeractive/pocket-mouse-film-quiz. The series also has two animations which will help to reinforce the concept. They can be accessed at http://www.hhmi.org/biointeractive/pocket-mouse-and-predation and http://www.hhmi.org/biointeractive/pocket-mouse-evolution.