1. Metabolic sensitivity to environmental temperature change increases in positive exponential relation with initial acclimated rates of energy expenditure, and is influenced by the relative rate with which intracellular amino acids are being mobilised by protein turnover.2. Greater metabolic sensitivity results in greater physiological variability with fluctuating temperatures, higher energy costs incurred during the response to temperature change, and reduced viability upon exposure to extreme high temperatures.3. These interrelations help explain the faster production and greater viability of multi-locus heterozygotes experimentally exposed to increased temperature and other stressors, as well as ecogeographical associations indicating the superiority of multi-locus heterozygotes in heterogeneous environments.4. Implications are discussed for understanding the effects of temperature change on ectotherm metabolism and evolution.