Traditionally, physiology practicals were an opportunity for students to observe physiological principles in action while gaining laboratory skills. In recent decades however, the call to teach students how to think like scientists, coupled with growing resistance to the use of vertebrate animals in the classic experiments, has led to the development of inquiry-based practicals that rely on invertebrate and plant model systems. These model systems can be used to demonstrate most of the same physiological principles as the vertebrate models while simultaneously developing student appreciation for the conservation of fundamental mechanisms throughout the animal and plant kingdoms. By eliminating the use of vertebrate animals, we avoid ethical issues (although we still stress appropriate handling and anesthesia of the animals) and supply problems while enhancing the ability of students to run multiple replicates rather than being limited to an n of 1 in their experiments. In the guided inquiry format, students are given some parameters (e.g., design an experiment to show the influence of extracellular Ca2+ on smooth muscle contraction) and a list of available equipment and supplies. They research the literature, design a protocol, execute it, analyse the data, and communicate their findings orally or in writing (1). Invertebrate model systems can be used for many neurobiology experiments (2). Crawfish (Procambarus clarkii) hearts substitute for frog hearts. Rat intestinal or uterine smooth muscle is replaced by earthworm (Lumbricus sp.) crop-gizzard preparations. In these heart and smooth muscle experiments students can apply neurotransmitters and various pharmacological agents to elicit effects. Renal tubule transport is easily visualized in Malpighian tubule preparations from crickets (Acheta domesticus) or cockroaches (Periplaneta americana or other species) and uses many of the same transporters as vertebrate kidney (3). Plant material such as pumpkin (Cucurbita sp.), privet (Ligustrum sp.), and peas (Pisum sp) can be used in experiments demonstrating osmolarity and tonicity, membrane transport, environmental effects on oxygen consumption, and enzyme activity (e.g., catalase). These non-vertebrate model systems have proved more acceptable to students. The organisms used are cultured for food or other commercial uses or can be bred in colonies within the laboratory. Anesthesia consists of cold or immersion in ethanol, which avoids the use of controlled substances. With the greater availability and lower cost of these model organisms, students are able to repeat their experiments enough times to do statistical analysis of the data. Overall, the use of non-vertebrate model systems in physiology practical teaching has supported active learning of physiological concepts and development of scientific thought processes and skills.