INSULIN in vitro fails to restore normal rates of glucose uptake, glucolysis and glucose oxidation in the alloxan–diabetic rat heart. This insulin resistance is reversed by hypophysectomy or adrenalectomy, and it may be caused by the inhibition of hexokinase, phosphofructokinase and pyruvate dehydrogenase^1,2. Similar changes may be induced in hearts from non-diabetic rats by in vitro perfusion with fatty acids, so it has been suggested that these changes in the diabetic heart are a consequence of increased rates of hydrolysis of muscle triglyceride and oxidation of fatty acid^2,3. Attempts to substantiate this suggestion by the use of known antilipolytic drugs were frustrated by their low activity in muscle preparations. The effect of fatty acids may depend on their oxidation leading to elevated tissue concentrations of acetyl CoA and citrate which may inhibit pyruvate dehydrogenase, phosphofructokinase and hexokinase². This suggested an alternative approach using inhibitors of fatty acid oxidation and in particular inhibitors of carnitine acyl transferase because of the apparently specific role of this enzyme in fatty acid oxidation. Acyl D-carnitines, which are potent inhibitors of the transferase, were unsuitable because of their toxicity. Tubbs and Chase⁴ have described inhibition of carnitine acyl transferase and of fatty acid oxidation in mitochondria with coenzyme A derivatives of 2-bromostearate and 2-bromolaurate. Conditions have been defined in which 2-bromostearate can be used as an inhibitor of fatty acid oxidation in the perfused heart, and these results are described here.