In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ~20 screens of information, on the subjects of the CO[subscript 2]-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed. For the learning modules, the interactive, active learning activities were primarily step-by-step learner control of explanations of complex physiological concepts, usually presented graphically. For the clinical cases, the active learning activities were primarily question-and-answer exercises that related clinical findings to the relevant basic science concepts. The student response was remarkably positive, with the interactive, active learning aspect of the instruction cited as the most important feature. Also, students cited the self-paced instruction, extensive use of interactive graphics, and side-by-side presentation of text and graphics as positive features. Most students reported that it took less time to study the subject matter with this online instruction compared with subject matter presented in the lecture hall. However, the approach to learning was highly examination driven, with most students delaying the study of the subject matter until a few days before the scheduled examination. Wider implementation of active learning computer-assisted instruction will require that instructors present subject matter interactively, that students fully embrace the responsibilities of independent learning, and that institutional administrations measure instructional effort by criteria other than scheduled hours of instruction.