Enzymes are able to handle the energy derived from the hydrolysis of phosphate compounds in such a way as to determine the parcel that is used for work and the fraction that is converted into heat. The sarco/endoplasmic reticulum Ca 2+ -ATPases (SERCA) is a family of membrane-bound ATPases that are able to transport Ca 2+ ion across the membrane using the chemical energy derived from ATP hydrolysis. The heat released during ATP hydrolysis by SERCA may vary from 10 up to 30 kcal/mol depending on the SERCA isoform used and on whether or not a Ca 2+ gradient is formed across the membrane. Drugs such as heparin, dimethyl sulfoxide and the platelet-activating factor (PAF) are able to modify the fraction of the chemical energy released during ATP hydrolysis that is used for Ca 2+ transport and the fraction that is dissipated in the surrounding medium as heat. The thyroid hormone 3,5,3′-triiodo l -thyronine (T 3 ) regulates the expression and function of the thermogenic SERCA isoforms. Modulation of heat production by SERCA might be one of the mechanisms involved in the increased thermogenesis found in hyperthyroidism.