Measurement of cardiac glucose oxidation (as a percentage of CO2 production) was made using the technique of infusion of 14C-D-glucose, together with measurement of 14CO2 and total CO2 produced by the myocardium. The measurements were made in 16 dogs under chloralose anaesthesia, before and after an i.v. injection of S-4-hydroxyphenylglycine (16.7 mg X kg-1, Oxfenicine: Pfizer). In one group of dogs circulating free-fatty-acid (FFA) levels were raised by infusion of intralipid heparin; in the other, circulating lactate was increased by infusion of 5 MNa-lactate (pH 7.0). In the last group of dogs the action of the drug was studied in cardiac denervated dogs. In the dogs with normal circulating substrate levels, Oxfenicine increased the glucose oxidation from 17.3 to 39.9% of total substrate oxidized. This was also the case in those dogs with high circulating FFA (9.0 to 32.3%). However, in dogs with high circulating lactate (over 5.0 mmol X l-1) the oxidation of glucose was relatively unaffected (2.0 to 7.1%). In cardiac denervated dogs, with a known inhibition of glycolysis, Oxfenicine increased glucose oxidation from 4.8 to 23.5%. These results show that Oxfenicine is able to switch the heart from the oxidation of fat to glucose or lactate as fuel.