The Homeostasis Concept Inventory (HCI) is a validated instrument for measuring students' knowledge of homeostasis. It is comprised of 20 multiple-choice questions covering key components of the previously validated Homeostasis Conceptual Framework (HCF). In this paper, we present the first multi-institutional study of the impact of physiology instruction on students' HCI performance. Five cohorts of physiology or anatomy and physiology (A&P) students at four academic institutions took the HCI both at the start of their academic term (pretest) and at the end of their term (posttest). Statistically significant but relatively modest improvements in overall scores were seen from pretest to posttest. Among the 20 questions, 8 questions had incorrect choices identified as "attractive distractors" on the pretest, meaning that they were chosen at higher-than-random frequencies. From pretest to posttest, there were only modest declines in selections of incorrect answers generally and of attractive distractors in particular. Three attractive distractors that all target one specific misconception, that homeostatic mechanisms are active only when a regulated variable is not at its setpoint, remained persistently attractive except for students of one instructor who directly addressed that misconception in lecture and lab. These data are sobering in that they show a limited impact of instruction on HCI performance. However, these data also include encouraging evidence that instructional targeting of a specific misconception may help students overcome that misconception.