Regulation of intracellular and extracellular pH is a fundamental homeostatic requirement for vertebrates, and metabolic perturbations to an animal’s acid-base status are primarily compensated by adjusting ventilation. Ventilation is controlled via negative feedback with O2, CO2, and pH as primary signals; peripheral (arterial) and central (brainstem) chemoreceptors sense these signals through activation of CO2/pH-sensitive neurons; respiratory rhythm is set in the integrator and modulated by negative feedback control via the breathing muscles (effectors). These feedback systems have been most fully elucidated for mammals where constant pH is normal, chemosensory structures are well defined, and the cellular mechanisms underlying chemosensitivity are under active investigation. In contrast, a significant gap in our knowledge of ventilatory control is that we know relatively little of the rhythm generation nor fundamental cellular mechanisms of individual chemosensitive neurons in poikilothermic vertebrates who have the additional acid-base regulation challenge of variable body temperatures (Tb). pH is inversely related to temperature, so an increase in Tb decreases pH and, conversely, a decrease in Tb increases pH; a-stat pH regulation maintains the ionization state of histidine residues (ΔpH/ΔT between -0.014 and -0.017 U/°C) (Reeves 1972). The degree to which pH changes with temperature varies for reptiles and amphibians; therefore, changes in Tb entail regulated, inversely proportional acid-base balance through adjusting ventilation. Vertebrate poikilothermy is not restricted to reptiles and amphibians. For example, birds and mammals may be significantly poikilothermic as juveniles, during torpor, and body temperature may even be ‘experimentally’ manipulated during induced hypothermia in endotherms, including humans. Poikilotherms experience substantial variation in body temperature (Tb) during their normal life histories and varying Tb can influence acid-base balance in a variety of ways. Dissociation of H+ ions from many compounds is temperature sensitive. Further, rates of cellular metabolism and, therefore, production of CO2 slow at lower temperatures, and physiological regulatory systems, including kidneys and lungs, are controlled by cells whose functions are also likely to vary with temperature. Given the fundamental importance of pH regulation, one might expect that poikilothermic vertebrates would have a well-defined set of neural respiratory control mechanisms to enable the regulation of temperature-dependent acid-base balance (da Silva, Glass et al. 2013). This question has long perplexed organismal physiologists since, despite the fundamental importance of pH homeostasis, the temperature-dependence of pH varies more than an order of magnitude between species of poikilothermic ectotherms, ranging from 0.001 pH U °C-1 in Savannah monitor lizards (Varanus exanthematicus) (Wood, Glass et al. 1977) to 0.03 pH U °C-1 in Spadefoot toads (Scaphiopus couchii) (Withers 1978). Regardless of the strategy used by the animal, regulation of pH requires an ability to sense pH perturbations within the brain and to adjust the depth and rhythm of breathing to appropriately regulate pH at temperature-specific values. Poikilotherms vary widely in pH regulatory strategies and in the patterns of ventilation induced by change in body temperature, but we know nothing of the mechanisms – in individual sensory neurons or in neural networks – that drive that variation. These animals thus provide an ideal model for studying the relation between cellular chemosensitive responses and respiratory pattern generation. In this symposium we address how differences in temperature dependence of central chemosensitive responses, both at the cellular and organismal level, shape ventilatory responses to temperature-induced metabolic challenges in vertebrates.