Students find it hard to understand acid-base homeostasis and the mechanisms involved in compensating for acid-base imbalances, including the role of the lungs and kidneys in this process. We have developed a laboratory activity based on collaborative problem-based learning and human patient simulators (HPSs) to teach this topic. Students (n=50) were divided into small groups and presented with five cases of acid-base imbalances simulated in HPSs. After recording various parameters including arterial blood gases, they collaborated in identifying the specific acid-base imbalance. An anonymous survey following the laboratory activity revealed that this laboratory improved their understanding of acid-base regulation (92%), improved quantitative understanding of acid-base physiology (90%), and improved understanding of acid-base imbalances (94%).