Diabetes mellitus (DM) was produced in 17 neonatal lambs by a single intravenous injection of alloxan monohydrate (150 mg/kg). All developed hyperglycemia (greater than 300 mg/100 ml) and glycosuria after 24 h, but none exhibited ketonuria or acidosis. Plasma insulin levels were reduced to about 20% of those appropriate for the plasma glucose levels. Glucose tolerance tests (intravenous) were also consistent with reduced insulin reserve. Measurements of left ventricular performance were obtained under constant hemodynamic conditions in 16 diabetics and did not differ from those in 10 normal lambs. However, myocardial uptake of glucose was sharply reduced and fatty acid uptake was less. Myocardial O2 consumption (MVO2) was unchanged. Coronary flow (CF) was significantly lower in the diabetics (P less than 0.001). Pressure-flow studies were also done and demonstrated a consistent reduction in CF at a given aortic pressure in DM compared with controls. These findings indicate that coronary vascular resistance is elevated in the lamb with DM, and this is not explained by a change in MVO2. Oxygen requirements of the diabetic hearts were satisfied by increased extraction.