This article reports on two studies investigating the use of computer-based stimuli that may then be used to develop activities and programming for students with profound multiple disabilities (PMD). Both studies used an alternating treatments design and systematic assessment strategy to present stimuli sequentially and to measure student responses to the varying computer-based stimuli. Study 1 compared student preferences for computer-based stimuli (individualized video programs and commercially available cause-and-effect software), which were then used in Study 2 to compare student preferences for stimuli presented on a traditional computer-based system and a large interactive whiteboard. Results support use of computer-based stimuli and video-based stimuli that may be used in the development and implementation of educational programs for students with PMD.