3-Hydroxy-3-methylglutaric acid administration to streptozotocin-diabetic rats produced a net decrease of plasma ketone bodies and triglycerides together with a slight decrease of total cholesterol. A nonsignificant enhancement of HDL-cholesterol and a negligible change in HDL-phospholipid was also observed. The effect of 3-hydroxy-3-methylglutarate was dose dependent and was more evident with the compound intraperitoneally injected than orally administered with drinking water. [14C]-3-hydroxy-3-methylglutarate was administered either orally or intraperitoneally both to diabetic and control groups of animals, and a higher radioactivity accumulated in liver and kidneys of diabetic rats compared to the controls. The possible mechanism of action of 3-hydroxy-3-methylglutarate is briefly discussed.