We present a new methodology for testing physiological responses of small organisms (size 70-500 microm) via changes in their oxygen respiration monitored by quenched-phosphorescence oxygen sensing on a scale of a single organism. The method is demonstrated using three different formats of respirometric assays, Artemia salina and mouse embryos as model animals, and various effectors including compounds that induce and prevent superoxide-mediated and heavy metal ion toxicity. These assays, which employ soluble oxygen probes, standard fluorescent readers, and accessorytools, provide sensitive, noninvasive, real-time monitoring of animal respiration, and rapid assessment of EC50, sublethal effects, and metabolic alterations. Applications include screening for acute toxicity of compound libraries and environmental samples, and the study of animal physiology and metabolism.